TY  - JOUR
AU  - Bajić, Vladan P.
AU  - Essack, Magbubah
AU  - Živković, Lada
AU  - Stewart, Alan J.
AU  - Zafirović, Sonja
AU  - Bajić, Vladimir B.
AU  - Gojobori, Takashi
AU  - Isenović, Esma R.
AU  - Spremo-Potparević, Biljana
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8825
AB  - Alzheimer’s disease (AD) is a neurodegenerative disease that affects millions of individuals worldwide and can occur relatively early or later in life. It is well known that genetic components, such as the amyloid precursor protein gene on chromosome 21, are fundamental in early-onset AD (EOAD). To date, however, only the apolipoprotein E4 (ApoE4) gene has been proved to be a genetic risk factor for late-onset AD (LOAD). In recent years, despite the hypothesis that many additional unidentified genes are likely to play a role in AD development, it is surprising that additional gene polymorphisms associated with LOAD have failed to come to light. In this review, we examine the role of X chromosome epigenetics and, based upon GWAS studies, the PCDHX11 gene. Furthermore, we explore other genetic risk factors of AD that involve X-chromosome epigenetics. © Copyright © 2020 Bajic, Essack, Zivkovic, Stewart, Zafirovic, Bajic, Gojobori, Isenovic and Spremo-Potparevic.
T2  - Frontiers in Genetics
T1  - The X Files: “The Mystery of X Chromosome Instability in Alzheimer’s Disease”
VL  - 10
DO  - 10.3389/fgene.2019.01368
ER  - 

@article{
author = "Bajić, Vladan P. and Essack, Magbubah and Živković, Lada and Stewart, Alan J. and Zafirović, Sonja and Bajić, Vladimir B. and Gojobori, Takashi and Isenović, Esma R. and Spremo-Potparević, Biljana",
year = "2020",
abstract = "Alzheimer’s disease (AD) is a neurodegenerative disease that affects millions of individuals worldwide and can occur relatively early or later in life. It is well known that genetic components, such as the amyloid precursor protein gene on chromosome 21, are fundamental in early-onset AD (EOAD). To date, however, only the apolipoprotein E4 (ApoE4) gene has been proved to be a genetic risk factor for late-onset AD (LOAD). In recent years, despite the hypothesis that many additional unidentified genes are likely to play a role in AD development, it is surprising that additional gene polymorphisms associated with LOAD have failed to come to light. In this review, we examine the role of X chromosome epigenetics and, based upon GWAS studies, the PCDHX11 gene. Furthermore, we explore other genetic risk factors of AD that involve X-chromosome epigenetics. © Copyright © 2020 Bajic, Essack, Zivkovic, Stewart, Zafirovic, Bajic, Gojobori, Isenovic and Spremo-Potparevic.",
journal = "Frontiers in Genetics",
title = "The X Files: “The Mystery of X Chromosome Instability in Alzheimer’s Disease”",
volume = "10",
doi = "10.3389/fgene.2019.01368"
}

Bajić, V. P., Essack, M., Živković, L., Stewart, A. J., Zafirović, S., Bajić, V. B., Gojobori, T., Isenović, E. R.,& Spremo-Potparević, B.. (2020). The X Files: “The Mystery of X Chromosome Instability in Alzheimer’s Disease”. in Frontiers in Genetics, 10.
https://doi.org/10.3389/fgene.2019.01368

Bajić VP, Essack M, Živković L, Stewart AJ, Zafirović S, Bajić VB, Gojobori T, Isenović ER, Spremo-Potparević B. The X Files: “The Mystery of X Chromosome Instability in Alzheimer’s Disease”. in Frontiers in Genetics. 2020;10.
doi:10.3389/fgene.2019.01368 .

Bajić, Vladan P., Essack, Magbubah, Živković, Lada, Stewart, Alan J., Zafirović, Sonja, Bajić, Vladimir B., Gojobori, Takashi, Isenović, Esma R., Spremo-Potparević, Biljana, "The X Files: “The Mystery of X Chromosome Instability in Alzheimer’s Disease”" in Frontiers in Genetics, 10 (2020),
https://doi.org/10.3389/fgene.2019.01368 . .

TY  - JOUR
AU  - Zarić, Božidarka
AU  - Radovanović, Jelena N.
AU  - Gluvić, Zoran
AU  - Stewart, Alan J.
AU  - Essack, Magbubah
AU  - Motwalli, Olaa
AU  - Gojobori, Takashi
AU  - Isenović, Esma R.
PY  - 2020
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9681
AB  - Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists between alterations in amino acid (AA) metabolism and the development of atherosclerosis. Recent studies have reported positive correlations between levels of branched-chain amino acids (BCAAs) such as leucine, valine, and isoleucine in plasma and the occurrence of metabolic disturbances. Elevated serum levels of BCAAs indicate a high cardiometabolic risk. Thus, BCAAs may also impact atherosclerosis prevention and offer a novel therapeutic strategy for specific individuals at risk of coronary events. The metabolism of AAs, such as L-arginine, homoarginine, and L-tryptophan, is recognized as a critical regulator of vascular homeostasis. Dietary intake of homoarginine, taurine, and glycine can improve atherosclerosis by endothelium remodeling. Available data also suggest that the regulation of AA metabolism by indoleamine 2,3-dioxygenase (IDO) and arginases 1 and 2 are mediated through various immunological signals and that immunosuppressive AA metabolizing enzymes are promising therapeutic targets against atherosclerosis. Further clinical studies and basic studies that make use of animal models are required. Here we review recent data examining links between AA metabolism and the development of atherosclerosis.
T2  - Frontiers in Immunology
T1  - Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes
VL  - 11
SP  - 2341
DO  - 10.3389/fimmu.2020.551758
ER  - 

@article{
author = "Zarić, Božidarka and Radovanović, Jelena N. and Gluvić, Zoran and Stewart, Alan J. and Essack, Magbubah and Motwalli, Olaa and Gojobori, Takashi and Isenović, Esma R.",
year = "2020",
abstract = "Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists between alterations in amino acid (AA) metabolism and the development of atherosclerosis. Recent studies have reported positive correlations between levels of branched-chain amino acids (BCAAs) such as leucine, valine, and isoleucine in plasma and the occurrence of metabolic disturbances. Elevated serum levels of BCAAs indicate a high cardiometabolic risk. Thus, BCAAs may also impact atherosclerosis prevention and offer a novel therapeutic strategy for specific individuals at risk of coronary events. The metabolism of AAs, such as L-arginine, homoarginine, and L-tryptophan, is recognized as a critical regulator of vascular homeostasis. Dietary intake of homoarginine, taurine, and glycine can improve atherosclerosis by endothelium remodeling. Available data also suggest that the regulation of AA metabolism by indoleamine 2,3-dioxygenase (IDO) and arginases 1 and 2 are mediated through various immunological signals and that immunosuppressive AA metabolizing enzymes are promising therapeutic targets against atherosclerosis. Further clinical studies and basic studies that make use of animal models are required. Here we review recent data examining links between AA metabolism and the development of atherosclerosis.",
journal = "Frontiers in Immunology",
title = "Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes",
volume = "11",
pages = "2341",
doi = "10.3389/fimmu.2020.551758"
}

Zarić, B., Radovanović, J. N., Gluvić, Z., Stewart, A. J., Essack, M., Motwalli, O., Gojobori, T.,& Isenović, E. R.. (2020). Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes. in Frontiers in Immunology, 11, 2341.
https://doi.org/10.3389/fimmu.2020.551758

Zarić B, Radovanović JN, Gluvić Z, Stewart AJ, Essack M, Motwalli O, Gojobori T, Isenović ER. Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes. in Frontiers in Immunology. 2020;11:2341.
doi:10.3389/fimmu.2020.551758 .

Zarić, Božidarka, Radovanović, Jelena N., Gluvić, Zoran, Stewart, Alan J., Essack, Magbubah, Motwalli, Olaa, Gojobori, Takashi, Isenović, Esma R., "Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes" in Frontiers in Immunology, 11 (2020):2341,
https://doi.org/10.3389/fimmu.2020.551758 . .

TY  - JOUR
AU  - Jovanović, Aleksandra
AU  - Sudar, Emina
AU  - Obradović, Milan M.
AU  - Pitt, Samantha J.
AU  - Stewart, Alan J.
AU  - Zafirović, Sonja
AU  - Stanimirović, Julijana
AU  - Radak, Đorđe J.
AU  - Isenović, Esma R.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1678
AB  - Background: Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular disease. Oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. Methods: In the present study, female Wistar rats were fed a standard diet or a HF diet (42% fat) for 10 weeks. iNOS gene and protein expressions were measured in heart tissue. HF-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p LT 0.05), iNOS protein level by 248% (p LT 0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p LT 0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p LT 0.01) in HF-fed rats. Expression of the p50 subunit of nuclear factor-kappa B (NF kappa B-p50) in heart was increased by 77% (p LT 0.01) in HF-fed rats. Expression of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2 in HF-fed rats. Estrogen receptor-levels (by 50%; p LT 0.05) and serum oestradiol concentrations (by 35%; p LT 0.05) were shown to be significantly reduced in HF-fed rats. Results and Conclusion: Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NF kappa B-p50 proteins. Decreased levels of oestradiol and ER protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.
T2  - Current Vascular Pharmacology
T1  - Influence of a High-fat Diet on Cardiac iNOS in Female Rats
VL  - 15
IS  - 5
SP  - 491
EP  - 500
DO  - 10.2174/1570161114666161025101303
ER  - 

@article{
author = "Jovanović, Aleksandra and Sudar, Emina and Obradović, Milan M. and Pitt, Samantha J. and Stewart, Alan J. and Zafirović, Sonja and Stanimirović, Julijana and Radak, Đorđe J. and Isenović, Esma R.",
year = "2017",
abstract = "Background: Overexpression of inducible nitric oxide synthase (iNOS) is a key link between high-fat (HF) diet induced obesity and cardiovascular disease. Oestradiol has cardioprotective effects that may be mediated through reduction of iNOS activity/expression. Methods: In the present study, female Wistar rats were fed a standard diet or a HF diet (42% fat) for 10 weeks. iNOS gene and protein expressions were measured in heart tissue. HF-fed rats exhibited a significant increase in cardiac iNOS mRNA by 695% (p LT 0.05), iNOS protein level by 248% (p LT 0.01), without changes in nitrate/nitrite levels. Expression of CD36 protein in plasma membranes was increased by 37% (p LT 0.05), while the concentration of free fatty acids (FFA) was reduced by 25% (p LT 0.01) in HF-fed rats. Expression of the p50 subunit of nuclear factor-kappa B (NF kappa B-p50) in heart was increased by 77% (p LT 0.01) in HF-fed rats. Expression of protein kinase B (Akt) and extracellular signal-regulated kinases 1/2 (ERK1/2) were unchanged between the groups. There was a significant increase in the ratio of phospho-Akt/total Akt but not for phospho-ERK1/2/total ERK1/2 in HF-fed rats. Estrogen receptor-levels (by 50%; p LT 0.05) and serum oestradiol concentrations (by 35%; p LT 0.05) were shown to be significantly reduced in HF-fed rats. Results and Conclusion: Our results revealed that a HF diet led to increased iNOS expression, most likely via a mechanism involving Akt and NF kappa B-p50 proteins. Decreased levels of oestradiol and ER protein in the HF-fed group, in combination with increased iNOS levels are consistent with the hypothesis that oestradiol has a cardioprotective effect through its ability to regulate iNOS expression.",
journal = "Current Vascular Pharmacology",
title = "Influence of a High-fat Diet on Cardiac iNOS in Female Rats",
volume = "15",
number = "5",
pages = "491-500",
doi = "10.2174/1570161114666161025101303"
}

Jovanović, A., Sudar, E., Obradović, M. M., Pitt, S. J., Stewart, A. J., Zafirović, S., Stanimirović, J., Radak, Đ. J.,& Isenović, E. R.. (2017). Influence of a High-fat Diet on Cardiac iNOS in Female Rats. in Current Vascular Pharmacology, 15(5), 491-500.
https://doi.org/10.2174/1570161114666161025101303

Jovanović A, Sudar E, Obradović MM, Pitt SJ, Stewart AJ, Zafirović S, Stanimirović J, Radak ĐJ, Isenović ER. Influence of a High-fat Diet on Cardiac iNOS in Female Rats. in Current Vascular Pharmacology. 2017;15(5):491-500.
doi:10.2174/1570161114666161025101303 .

Jovanović, Aleksandra, Sudar, Emina, Obradović, Milan M., Pitt, Samantha J., Stewart, Alan J., Zafirović, Sonja, Stanimirović, Julijana, Radak, Đorđe J., Isenović, Esma R., "Influence of a High-fat Diet on Cardiac iNOS in Female Rats" in Current Vascular Pharmacology, 15, no. 5 (2017):491-500,
https://doi.org/10.2174/1570161114666161025101303 . .

TY  - JOUR
AU  - Zafirović, Sonja
AU  - Obradović, Milan M.
AU  - Sudar-Milovanović, Emina
AU  - Jovanović, Aleksandra
AU  - Stanimirović, Julijana
AU  - Stewart, Alan J.
AU  - Pitt, Samantha J.
AU  - Isenović, Esma R.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1520
AB  - The aim of this study was to investigate the in vivo effects of 17 beta-estradiol (E-2) on myocardial metabolism and inducible nitric oxide synthase (iNOS) expression/activity in obese rats. Male Wistar rats were fed with a normal or a high fat (HF) diet (42% fat) for 10 weeks. Half of the HF fed rats were treated with a single dose of E-2 while the other half were placebo-treated. 24 h after treatment animals were sacrificed. E-2 reduced cardiac free fatty acid (FFA) (p LT 0.05), L-arginine (p LT 0.01), iNOS mRNA (p LT 0.01), and protein (p LT 0.05) levels and translocation of the FFA transporter (CD36) (p LT 0.01) to the plasma membrane (PM) in HF fed rats. In contrast, Akt phosphorylation at Thr308 (p LT 0.05) and translocation of the glucose transporter GLUT4 (p LT 0.05) to the PM increased after E-2 treatment in HF rats. Our results indicate that E-2 acts via the PI3K/Akt signalling pathway to partially protect myocardial metabolism by attenuating the detrimental effects of increased iNOS expression/activity in HF fed rats. (C) 2017 Elsevier B.V. All rights reserved.
T2  - Molecular and Cellular Endocrinology
T1  - 17 beta-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats
VL  - 446
IS  - C
SP  - 12
EP  - 20
DO  - 10.1016/j.mce.2017.02.001
ER  - 

@article{
author = "Zafirović, Sonja and Obradović, Milan M. and Sudar-Milovanović, Emina and Jovanović, Aleksandra and Stanimirović, Julijana and Stewart, Alan J. and Pitt, Samantha J. and Isenović, Esma R.",
year = "2017",
abstract = "The aim of this study was to investigate the in vivo effects of 17 beta-estradiol (E-2) on myocardial metabolism and inducible nitric oxide synthase (iNOS) expression/activity in obese rats. Male Wistar rats were fed with a normal or a high fat (HF) diet (42% fat) for 10 weeks. Half of the HF fed rats were treated with a single dose of E-2 while the other half were placebo-treated. 24 h after treatment animals were sacrificed. E-2 reduced cardiac free fatty acid (FFA) (p LT 0.05), L-arginine (p LT 0.01), iNOS mRNA (p LT 0.01), and protein (p LT 0.05) levels and translocation of the FFA transporter (CD36) (p LT 0.01) to the plasma membrane (PM) in HF fed rats. In contrast, Akt phosphorylation at Thr308 (p LT 0.05) and translocation of the glucose transporter GLUT4 (p LT 0.05) to the PM increased after E-2 treatment in HF rats. Our results indicate that E-2 acts via the PI3K/Akt signalling pathway to partially protect myocardial metabolism by attenuating the detrimental effects of increased iNOS expression/activity in HF fed rats. (C) 2017 Elsevier B.V. All rights reserved.",
journal = "Molecular and Cellular Endocrinology",
title = "17 beta-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats",
volume = "446",
number = "C",
pages = "12-20",
doi = "10.1016/j.mce.2017.02.001"
}

Zafirović, S., Obradović, M. M., Sudar-Milovanović, E., Jovanović, A., Stanimirović, J., Stewart, A. J., Pitt, S. J.,& Isenović, E. R.. (2017). 17 beta-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats. in Molecular and Cellular Endocrinology, 446(C), 12-20.
https://doi.org/10.1016/j.mce.2017.02.001

Zafirović S, Obradović MM, Sudar-Milovanović E, Jovanović A, Stanimirović J, Stewart AJ, Pitt SJ, Isenović ER. 17 beta-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats. in Molecular and Cellular Endocrinology. 2017;446(C):12-20.
doi:10.1016/j.mce.2017.02.001 .

Zafirović, Sonja, Obradović, Milan M., Sudar-Milovanović, Emina, Jovanović, Aleksandra, Stanimirović, Julijana, Stewart, Alan J., Pitt, Samantha J., Isenović, Esma R., "17 beta-Estradiol protects against the effects of a high fat diet on cardiac glucose, lipid and nitric oxide metabolism in rats" in Molecular and Cellular Endocrinology, 446, no. C (2017):12-20,
https://doi.org/10.1016/j.mce.2017.02.001 . .

TY  - JOUR
AU  - Jovanović, Aleksandra
AU  - Obradović, Milan M.
AU  - Sudar-Milovanović, Emina
AU  - Stewart, Alan J.
AU  - Pitt, Samantha J.
AU  - Alavantić, Dragan
AU  - Aleksić, Ema
AU  - Isenović, Esma R.
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1812
AB  - The aim of this study was to investigate whether the presence of endogenous estradiol alters the effects of a high-fat (HF) diet on activity/expression of the cardiac Na+/K+-ATPase, via PI3K/IRS and RhoA/ROCK signalling cascades in female rats. For this study, female Wistar rats (8 weeks old, 150-200 g) were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. The results show that rats fed a HF diet exhibited a decrease in phosphorylation of the alpha(1) subunit of Na+/K+-ATPase by 30% (p LT 0.05), expression of total alpha(1) subunit of Na+/K+-ATPase by 31% (p LT 0.05), and association of IRS1 with p85 subunit of PI3K by 42% (p LT 0.05), while the levels of cardiac RhoA and ROCK2 were significantly increased by 84% (p LT 0.01) and 62% (p LT 0.05), respectively. Our results suggest that a HF diet alters cardiac Na+/K+-ATPase expression via molecular mechanisms involving RhoA/ROCK and IRS-1/PI3K signalling in female rats.
T2  - Molecular and Cellular Biochemistry
T1  - Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high-fat diet
VL  - 436
IS  - 1-2
SP  - 49
EP  - 58
DO  - 10.1007/s11010-017-3077-y
ER  - 

@article{
author = "Jovanović, Aleksandra and Obradović, Milan M. and Sudar-Milovanović, Emina and Stewart, Alan J. and Pitt, Samantha J. and Alavantić, Dragan and Aleksić, Ema and Isenović, Esma R.",
year = "2017",
abstract = "The aim of this study was to investigate whether the presence of endogenous estradiol alters the effects of a high-fat (HF) diet on activity/expression of the cardiac Na+/K+-ATPase, via PI3K/IRS and RhoA/ROCK signalling cascades in female rats. For this study, female Wistar rats (8 weeks old, 150-200 g) were fed a standard diet or a HF diet (balanced diet for laboratory rats enriched with 42% fat) for 10 weeks. The results show that rats fed a HF diet exhibited a decrease in phosphorylation of the alpha(1) subunit of Na+/K+-ATPase by 30% (p LT 0.05), expression of total alpha(1) subunit of Na+/K+-ATPase by 31% (p LT 0.05), and association of IRS1 with p85 subunit of PI3K by 42% (p LT 0.05), while the levels of cardiac RhoA and ROCK2 were significantly increased by 84% (p LT 0.01) and 62% (p LT 0.05), respectively. Our results suggest that a HF diet alters cardiac Na+/K+-ATPase expression via molecular mechanisms involving RhoA/ROCK and IRS-1/PI3K signalling in female rats.",
journal = "Molecular and Cellular Biochemistry",
title = "Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high-fat diet",
volume = "436",
number = "1-2",
pages = "49-58",
doi = "10.1007/s11010-017-3077-y"
}

Jovanović, A., Obradović, M. M., Sudar-Milovanović, E., Stewart, A. J., Pitt, S. J., Alavantić, D., Aleksić, E.,& Isenović, E. R.. (2017). Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high-fat diet. in Molecular and Cellular Biochemistry, 436(1-2), 49-58.
https://doi.org/10.1007/s11010-017-3077-y

Jovanović A, Obradović MM, Sudar-Milovanović E, Stewart AJ, Pitt SJ, Alavantić D, Aleksić E, Isenović ER. Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high-fat diet. in Molecular and Cellular Biochemistry. 2017;436(1-2):49-58.
doi:10.1007/s11010-017-3077-y .

Jovanović, Aleksandra, Obradović, Milan M., Sudar-Milovanović, Emina, Stewart, Alan J., Pitt, Samantha J., Alavantić, Dragan, Aleksić, Ema, Isenović, Esma R., "Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high-fat diet" in Molecular and Cellular Biochemistry, 436, no. 1-2 (2017):49-58,
https://doi.org/10.1007/s11010-017-3077-y . .

TY  - JOUR
AU  - Stanimirović, Julijana
AU  - Obradović, Milan M.
AU  - Jovanović, Aleksandra
AU  - Sudar, Emina
AU  - Zafirović, Sonja
AU  - Pitt, Samantha J.
AU  - Stewart, Alan J.
AU  - Isenović, Esma R.
PY  - 2016
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/1004
AB  - Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NF kappa B, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser(473) and Thr(308)), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NF kappa B-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr(308) and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR. (C) 2016 Elsevier Inc. All rights reserved.
PB  - Elsevier
T2  - Nitric Oxide: Biology and Chemistry
T1  - A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats
VL  - 54
SP  - 51
EP  - 59
DO  - 10.1016/j.niox.2016.02.007
ER  - 

@article{
author = "Stanimirović, Julijana and Obradović, Milan M. and Jovanović, Aleksandra and Sudar, Emina and Zafirović, Sonja and Pitt, Samantha J. and Stewart, Alan J. and Isenović, Esma R.",
year = "2016",
abstract = "Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NF kappa B, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser(473) and Thr(308)), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NF kappa B-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr(308) and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR. (C) 2016 Elsevier Inc. All rights reserved.",
publisher = "Elsevier",
journal = "Nitric Oxide: Biology and Chemistry",
title = "A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats",
volume = "54",
pages = "51-59",
doi = "10.1016/j.niox.2016.02.007"
}

Stanimirović, J., Obradović, M. M., Jovanović, A., Sudar, E., Zafirović, S., Pitt, S. J., Stewart, A. J.,& Isenović, E. R.. (2016). A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats. in Nitric Oxide: Biology and Chemistry
Elsevier., 54, 51-59.
https://doi.org/10.1016/j.niox.2016.02.007

Stanimirović J, Obradović MM, Jovanović A, Sudar E, Zafirović S, Pitt SJ, Stewart AJ, Isenović ER. A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats. in Nitric Oxide: Biology and Chemistry. 2016;54:51-59.
doi:10.1016/j.niox.2016.02.007 .

Stanimirović, Julijana, Obradović, Milan M., Jovanović, Aleksandra, Sudar, Emina, Zafirović, Sonja, Pitt, Samantha J., Stewart, Alan J., Isenović, Esma R., "A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats" in Nitric Oxide: Biology and Chemistry, 54 (2016):51-59,
https://doi.org/10.1016/j.niox.2016.02.007 . .

TY  - JOUR
AU  - Obradović, Milan M.
AU  - Stewart, Alan J.
AU  - Pitt, Samantha J.
AU  - Labudović-Borović, Milica
AU  - Sudar, Emina
AU  - Petrovic, Voin
AU  - Zafirović, Sonja
AU  - Maravić-Stojković, Vera
AU  - Vasić, Vesna M.
AU  - Isenović, Esma R.
PY  - 2014
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5989
AB  - In this study the in vivo effects of estradiol in regulating Na+/K+-ATPase function in rat heart was studied. Adult male Wistar rats were treated with estradiol (40 mu g/kg, i.p.) and after 24 h the animals were sacrificed and the heart excised. Following estradiol administration, cardiac Na+/K(+)ATPase activity, expression of the alpha l subunit, and phosphorylation of the al subunit were significantly increased. These animals also had significantly decreased levels of digoxin-like immunoreactive factor(s). Na+ levels were also significantly reduced but to a level that was still within the normal physiological range, highlighting the ability of the Na+/K+-ATPase to balance the ionic composition following treatment with estradiol. Estradiol treated rats also showed increased phosphorylation of protein kinase B (Akt), and extracellular-signal-regulated kinase 1/2 (ERK1/2). We therefore suggest a role for Akt and/or ERK1/2 in estradiol-mediated regulation of cardiac Na+/K+-ATPase expression and activity in rat heart. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
T2  - Molecular and Cellular Endocrinology
T1  - In vivo effects of 17 beta-estradiol on cardiac Na+/K+-ATPase expression and activity in rat heart
VL  - 388
IS  - 1-2
SP  - 58
EP  - 68
DO  - 10.1016/j.mce.2014.03.005
ER  - 

@article{
author = "Obradović, Milan M. and Stewart, Alan J. and Pitt, Samantha J. and Labudović-Borović, Milica and Sudar, Emina and Petrovic, Voin and Zafirović, Sonja and Maravić-Stojković, Vera and Vasić, Vesna M. and Isenović, Esma R.",
year = "2014",
abstract = "In this study the in vivo effects of estradiol in regulating Na+/K+-ATPase function in rat heart was studied. Adult male Wistar rats were treated with estradiol (40 mu g/kg, i.p.) and after 24 h the animals were sacrificed and the heart excised. Following estradiol administration, cardiac Na+/K(+)ATPase activity, expression of the alpha l subunit, and phosphorylation of the al subunit were significantly increased. These animals also had significantly decreased levels of digoxin-like immunoreactive factor(s). Na+ levels were also significantly reduced but to a level that was still within the normal physiological range, highlighting the ability of the Na+/K+-ATPase to balance the ionic composition following treatment with estradiol. Estradiol treated rats also showed increased phosphorylation of protein kinase B (Akt), and extracellular-signal-regulated kinase 1/2 (ERK1/2). We therefore suggest a role for Akt and/or ERK1/2 in estradiol-mediated regulation of cardiac Na+/K+-ATPase expression and activity in rat heart. (C) 2014 Elsevier Ireland Ltd. All rights reserved.",
journal = "Molecular and Cellular Endocrinology",
title = "In vivo effects of 17 beta-estradiol on cardiac Na+/K+-ATPase expression and activity in rat heart",
volume = "388",
number = "1-2",
pages = "58-68",
doi = "10.1016/j.mce.2014.03.005"
}

Obradović, M. M., Stewart, A. J., Pitt, S. J., Labudović-Borović, M., Sudar, E., Petrovic, V., Zafirović, S., Maravić-Stojković, V., Vasić, V. M.,& Isenović, E. R.. (2014). In vivo effects of 17 beta-estradiol on cardiac Na+/K+-ATPase expression and activity in rat heart. in Molecular and Cellular Endocrinology, 388(1-2), 58-68.
https://doi.org/10.1016/j.mce.2014.03.005

Obradović MM, Stewart AJ, Pitt SJ, Labudović-Borović M, Sudar E, Petrovic V, Zafirović S, Maravić-Stojković V, Vasić VM, Isenović ER. In vivo effects of 17 beta-estradiol on cardiac Na+/K+-ATPase expression and activity in rat heart. in Molecular and Cellular Endocrinology. 2014;388(1-2):58-68.
doi:10.1016/j.mce.2014.03.005 .

Obradović, Milan M., Stewart, Alan J., Pitt, Samantha J., Labudović-Borović, Milica, Sudar, Emina, Petrovic, Voin, Zafirović, Sonja, Maravić-Stojković, Vera, Vasić, Vesna M., Isenović, Esma R., "In vivo effects of 17 beta-estradiol on cardiac Na+/K+-ATPase expression and activity in rat heart" in Molecular and Cellular Endocrinology, 388, no. 1-2 (2014):58-68,
https://doi.org/10.1016/j.mce.2014.03.005 . .

TY  - JOUR
AU  - Obradović, Milan M.
AU  - Bjelogrlic, Predrag
AU  - Rizzo, Manfredi
AU  - Katsiki, Niki
AU  - Haidara, Mohamed A.
AU  - Stewart, Alan J.
AU  - Jovanović, Aleksandra
AU  - Isenović, Esma R.
PY  - 2013
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/5672
AB  - Obesity is associated with aberrant sodium/potassium-ATPase (Na+/K+-ATPase) activity, apparently linked to hyperglycemic hyperinsulinemia, which may repress or inactivate the enzyme. The reduction of Na+/K+-ATPase activity in cardiac tissue induces myocyte death and cardiac dysfunction, leading to the development of myocardial dilation in animal models; this has also been documented in patients with heart failure (HF). During several pathological situations (cardiac insufficiency and HF) and in experimental models (obesity), the heart becomes more sensitive to the effect of cardiac glycosides, due to a decrease in Na+/K+-ATPase levels. The primary female sex steroid estradiol has long been recognized to be important in a wide variety of physiological processes. Numerous studies, including ours, have shown that estradiol is one of the major factors controlling the activity and expression of Na+/K+-ATPase in the cardiovascular (CV) system. However, the effects of estradiol on Na+/K+-ATPase in both normal and pathological conditions, such as obesity, remain unclear. Increasing our understanding of the molecular mechanisms by which estradiol mediates its effects on Na+/K+-ATPase function may help to develop new strategies for the treatment of CV diseases. Herein, we discuss the latest data from animal and clinical studies that have examined how pathophysiological conditions such as obesity and the action of estradiol regulate Na+/K+-ATPase activity.
T2  - Journal of Endocrinology
T1  - Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases
VL  - 218
IS  - 3
SP  - R13
EP  - R23
DO  - 10.1530/JOE-13-0144
ER  - 

@article{
author = "Obradović, Milan M. and Bjelogrlic, Predrag and Rizzo, Manfredi and Katsiki, Niki and Haidara, Mohamed A. and Stewart, Alan J. and Jovanović, Aleksandra and Isenović, Esma R.",
year = "2013",
abstract = "Obesity is associated with aberrant sodium/potassium-ATPase (Na+/K+-ATPase) activity, apparently linked to hyperglycemic hyperinsulinemia, which may repress or inactivate the enzyme. The reduction of Na+/K+-ATPase activity in cardiac tissue induces myocyte death and cardiac dysfunction, leading to the development of myocardial dilation in animal models; this has also been documented in patients with heart failure (HF). During several pathological situations (cardiac insufficiency and HF) and in experimental models (obesity), the heart becomes more sensitive to the effect of cardiac glycosides, due to a decrease in Na+/K+-ATPase levels. The primary female sex steroid estradiol has long been recognized to be important in a wide variety of physiological processes. Numerous studies, including ours, have shown that estradiol is one of the major factors controlling the activity and expression of Na+/K+-ATPase in the cardiovascular (CV) system. However, the effects of estradiol on Na+/K+-ATPase in both normal and pathological conditions, such as obesity, remain unclear. Increasing our understanding of the molecular mechanisms by which estradiol mediates its effects on Na+/K+-ATPase function may help to develop new strategies for the treatment of CV diseases. Herein, we discuss the latest data from animal and clinical studies that have examined how pathophysiological conditions such as obesity and the action of estradiol regulate Na+/K+-ATPase activity.",
journal = "Journal of Endocrinology",
title = "Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases",
volume = "218",
number = "3",
pages = "R13-R23",
doi = "10.1530/JOE-13-0144"
}

Obradović, M. M., Bjelogrlic, P., Rizzo, M., Katsiki, N., Haidara, M. A., Stewart, A. J., Jovanović, A.,& Isenović, E. R.. (2013). Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases. in Journal of Endocrinology, 218(3), R13-R23.
https://doi.org/10.1530/JOE-13-0144

Obradović MM, Bjelogrlic P, Rizzo M, Katsiki N, Haidara MA, Stewart AJ, Jovanović A, Isenović ER. Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases. in Journal of Endocrinology. 2013;218(3):R13-R23.
doi:10.1530/JOE-13-0144 .

Obradović, Milan M., Bjelogrlic, Predrag, Rizzo, Manfredi, Katsiki, Niki, Haidara, Mohamed A., Stewart, Alan J., Jovanović, Aleksandra, Isenović, Esma R., "Effects of obesity and estradiol on Na+/K+-ATPase and their relevance to cardiovascular diseases" in Journal of Endocrinology, 218, no. 3 (2013):R13-R23,
https://doi.org/10.1530/JOE-13-0144 . .