TY  - JOUR
AU  - Bitar, Milad S.
AU  - Ayed, Adel K.
AU  - Abdel-Halim, Samy M.
AU  - Isenović, Esma R.
AU  - Al-Mulla, Fahd
PY  - 2010
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/4010
AB  - Aims: Endothelial dysfunction is a key triggering event in the development of cardiovascular diseases and the current study explored this phenomenon in the context of inflammation, apoptosis, reactive oxygen species (ROS) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during chronic diabetes. Main methods: alpha-Lipoic acid (ALA) and wortmannin (WM) were chronically administered to aged Goto Kakizaki (GK) rats, a genetic model of non-obese type II diabetes. Key indices of inflammation, apoptosis and oxidative stress were assessed using western blotting, real-time PCR and immunofluoresence-based techniques. Key findings: A chronic inflammation (e.g., increased mRNA/protein levels of INF-alpha, ICAM, fractalkine, CD-68, myeloperoxidase) in connection with increased caspase-based apoptotic cell death and heightened state of oxidative stress (HSOS)- appear to exist in diabetic cardiovascular tissues. An assessment of NF-kappa B dynamics in aged diabetic vessels revealed not only a marked increase in cytosolic phosphorylated levels of I kappa B-alpha, NIK, IRK but also an enhancement in nuclear localization of p65 concomitantly with augmented NF-kappa B-DNA binding activity. Most of the aforementioned cardiovascular-based diabetic abnormalities including reduced activities of PI3K and Akt kinase were ameliorated following chronic ALA therapy. WM, given to GK rats negated the anti-inflammatory and anti-apoptotic actions of ALA. Significance: Our data highlight a unifying mechanism whereby HSOS through an induction of NF-kappa B activity together with an impairment in PI3K/Akt pathway favors pro-inflammatory/pro-apoptotic diabetic vascular milieu that culminate in the onset of endothelial dysfunction, a phenomenon which appears to be amenable to treatment with antioxidants and/or PI3/Akt mimetics (e.g., ALA). (C) 2010 Elsevier Inc. All rights reserved.
T2  - Life Sciences
T1  - Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism
VL  - 86
IS  - 23-24
SP  - 844
EP  - 853
DO  - 10.1016/j.lfs.2010.03.019
ER  - 

@article{
author = "Bitar, Milad S. and Ayed, Adel K. and Abdel-Halim, Samy M. and Isenović, Esma R. and Al-Mulla, Fahd",
year = "2010",
abstract = "Aims: Endothelial dysfunction is a key triggering event in the development of cardiovascular diseases and the current study explored this phenomenon in the context of inflammation, apoptosis, reactive oxygen species (ROS) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during chronic diabetes. Main methods: alpha-Lipoic acid (ALA) and wortmannin (WM) were chronically administered to aged Goto Kakizaki (GK) rats, a genetic model of non-obese type II diabetes. Key indices of inflammation, apoptosis and oxidative stress were assessed using western blotting, real-time PCR and immunofluoresence-based techniques. Key findings: A chronic inflammation (e.g., increased mRNA/protein levels of INF-alpha, ICAM, fractalkine, CD-68, myeloperoxidase) in connection with increased caspase-based apoptotic cell death and heightened state of oxidative stress (HSOS)- appear to exist in diabetic cardiovascular tissues. An assessment of NF-kappa B dynamics in aged diabetic vessels revealed not only a marked increase in cytosolic phosphorylated levels of I kappa B-alpha, NIK, IRK but also an enhancement in nuclear localization of p65 concomitantly with augmented NF-kappa B-DNA binding activity. Most of the aforementioned cardiovascular-based diabetic abnormalities including reduced activities of PI3K and Akt kinase were ameliorated following chronic ALA therapy. WM, given to GK rats negated the anti-inflammatory and anti-apoptotic actions of ALA. Significance: Our data highlight a unifying mechanism whereby HSOS through an induction of NF-kappa B activity together with an impairment in PI3K/Akt pathway favors pro-inflammatory/pro-apoptotic diabetic vascular milieu that culminate in the onset of endothelial dysfunction, a phenomenon which appears to be amenable to treatment with antioxidants and/or PI3/Akt mimetics (e.g., ALA). (C) 2010 Elsevier Inc. All rights reserved.",
journal = "Life Sciences",
title = "Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism",
volume = "86",
number = "23-24",
pages = "844-853",
doi = "10.1016/j.lfs.2010.03.019"
}

Bitar, M. S., Ayed, A. K., Abdel-Halim, S. M., Isenović, E. R.,& Al-Mulla, F.. (2010). Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism. in Life Sciences, 86(23-24), 844-853.
https://doi.org/10.1016/j.lfs.2010.03.019

Bitar MS, Ayed AK, Abdel-Halim SM, Isenović ER, Al-Mulla F. Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism. in Life Sciences. 2010;86(23-24):844-853.
doi:10.1016/j.lfs.2010.03.019 .

Bitar, Milad S., Ayed, Adel K., Abdel-Halim, Samy M., Isenović, Esma R., Al-Mulla, Fahd, "Inflammation and apoptosis in aortic tissues of aged type II diabetes: Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism" in Life Sciences, 86, no. 23-24 (2010):844-853,
https://doi.org/10.1016/j.lfs.2010.03.019 . .