Involvement of PI3K, Akt and RhoA in Oestradiol Regulation of Cardiac iNOS Expression
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Аутори
Zafirović, SonjaSudar-Milovanović, Emina
Obradović, Milan M.
Đorđević, Jelena D.
Jasnić, Nebojša
Labudović-Borović, Milica
Isenović, Esma R.
Чланак у часопису (Објављена верзија)
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© Bentham Science Publishers
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BACKGROUND: Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. METHODS: Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectrophotometrically. For protein expressions of iNOS, p65 subunit of nuclear factor-κB (NFκB-p65), Ras homolog gene family-member A (RhoA), angiotensin II receptor type 1 (AT1R), insulin receptor substrate 1 (IRS-1), p85, p110 and protein kinase B (Akt), Western blot method was used. Coimmunoprecipitation was used for measuring the association of IRS-1 with the p85 subunit of phosphatidylinositol- 3-kinase (PI3K). The expression of iNOS messenger ribonucleic acid (mRNA) was measured with the quantitative ...real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of the tissue was used to detect localization and expression of iNOS in heart tissue. RESULTS: Oestradiol treatment reduced L-Arg concentration (p<0.01), iNOS mRNA (p<0.01) and protein (p<0.001) expression, level of RhoA (p<0.05) and AT1R (p<0.001) protein. In contrast, plasma NO (p<0.05), Akt phosphorylation at Thr308 (p<0.05) and protein level of p85 (p<0.001) increased after oestradiol treatment. CONCLUSION: Our results suggest that oestradiol in vivo regulates cardiac iNOS expression via the PI3K/Akt signaling pathway, through attenuation of RhoA and AT1R.
Кључне речи:
Cardioprotection / oestradiol / rat heart / inducible nitric oxide synthase / eNOS / CVSИзвор:
Current Vascular Pharmacology, 2019, 17, 3, 307-318Финансирање / пројекти:
- Хормонска регулација експресије и активности азот оксид синтазе и натријум-калијумове пумпе у експерименталним моделима инсулинске резистенције, дијабетеса и кардиоваскуларних поремећаја (RS-MESTD-Basic Research (BR or ON)-173033)
- Ефекат метаболичких и неметаболичких стресора на експресију и деловање неуроендокриних регулатора енергетске хомеостазе (RS-MESTD-Basic Research (BR or ON)-173023)
DOI: 10.2174/1570161116666180212142414
ISSN: 1570-1611; 1875-6212
PubMed: 29437011
WoS: 000459679900011
Scopus: 2-s2.0-85062634673
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Институција/група
VinčaTY - JOUR AU - Zafirović, Sonja AU - Sudar-Milovanović, Emina AU - Obradović, Milan M. AU - Đorđević, Jelena D. AU - Jasnić, Nebojša AU - Labudović-Borović, Milica AU - Isenović, Esma R. PY - 2019 UR - http://www.eurekaselect.com/159734/article UR - https://vinar.vin.bg.ac.rs/handle/123456789/8097 AB - BACKGROUND: Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. METHODS: Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectrophotometrically. For protein expressions of iNOS, p65 subunit of nuclear factor-κB (NFκB-p65), Ras homolog gene family-member A (RhoA), angiotensin II receptor type 1 (AT1R), insulin receptor substrate 1 (IRS-1), p85, p110 and protein kinase B (Akt), Western blot method was used. Coimmunoprecipitation was used for measuring the association of IRS-1 with the p85 subunit of phosphatidylinositol- 3-kinase (PI3K). The expression of iNOS messenger ribonucleic acid (mRNA) was measured with the quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of the tissue was used to detect localization and expression of iNOS in heart tissue. RESULTS: Oestradiol treatment reduced L-Arg concentration (p<0.01), iNOS mRNA (p<0.01) and protein (p<0.001) expression, level of RhoA (p<0.05) and AT1R (p<0.001) protein. In contrast, plasma NO (p<0.05), Akt phosphorylation at Thr308 (p<0.05) and protein level of p85 (p<0.001) increased after oestradiol treatment. CONCLUSION: Our results suggest that oestradiol in vivo regulates cardiac iNOS expression via the PI3K/Akt signaling pathway, through attenuation of RhoA and AT1R. T2 - Current Vascular Pharmacology T1 - Involvement of PI3K, Akt and RhoA in Oestradiol Regulation of Cardiac iNOS Expression VL - 17 IS - 3 SP - 307 EP - 318 DO - 10.2174/1570161116666180212142414 ER -
@article{ author = "Zafirović, Sonja and Sudar-Milovanović, Emina and Obradović, Milan M. and Đorđević, Jelena D. and Jasnić, Nebojša and Labudović-Borović, Milica and Isenović, Esma R.", year = "2019", abstract = "BACKGROUND: Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. METHODS: Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectrophotometrically. For protein expressions of iNOS, p65 subunit of nuclear factor-κB (NFκB-p65), Ras homolog gene family-member A (RhoA), angiotensin II receptor type 1 (AT1R), insulin receptor substrate 1 (IRS-1), p85, p110 and protein kinase B (Akt), Western blot method was used. Coimmunoprecipitation was used for measuring the association of IRS-1 with the p85 subunit of phosphatidylinositol- 3-kinase (PI3K). The expression of iNOS messenger ribonucleic acid (mRNA) was measured with the quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of the tissue was used to detect localization and expression of iNOS in heart tissue. RESULTS: Oestradiol treatment reduced L-Arg concentration (p<0.01), iNOS mRNA (p<0.01) and protein (p<0.001) expression, level of RhoA (p<0.05) and AT1R (p<0.001) protein. In contrast, plasma NO (p<0.05), Akt phosphorylation at Thr308 (p<0.05) and protein level of p85 (p<0.001) increased after oestradiol treatment. CONCLUSION: Our results suggest that oestradiol in vivo regulates cardiac iNOS expression via the PI3K/Akt signaling pathway, through attenuation of RhoA and AT1R.", journal = "Current Vascular Pharmacology", title = "Involvement of PI3K, Akt and RhoA in Oestradiol Regulation of Cardiac iNOS Expression", volume = "17", number = "3", pages = "307-318", doi = "10.2174/1570161116666180212142414" }
Zafirović, S., Sudar-Milovanović, E., Obradović, M. M., Đorđević, J. D., Jasnić, N., Labudović-Borović, M.,& Isenović, E. R.. (2019). Involvement of PI3K, Akt and RhoA in Oestradiol Regulation of Cardiac iNOS Expression. in Current Vascular Pharmacology, 17(3), 307-318. https://doi.org/10.2174/1570161116666180212142414
Zafirović S, Sudar-Milovanović E, Obradović MM, Đorđević JD, Jasnić N, Labudović-Borović M, Isenović ER. Involvement of PI3K, Akt and RhoA in Oestradiol Regulation of Cardiac iNOS Expression. in Current Vascular Pharmacology. 2019;17(3):307-318. doi:10.2174/1570161116666180212142414 .
Zafirović, Sonja, Sudar-Milovanović, Emina, Obradović, Milan M., Đorđević, Jelena D., Jasnić, Nebojša, Labudović-Borović, Milica, Isenović, Esma R., "Involvement of PI3K, Akt and RhoA in Oestradiol Regulation of Cardiac iNOS Expression" in Current Vascular Pharmacology, 17, no. 3 (2019):307-318, https://doi.org/10.2174/1570161116666180212142414 . .