Tags

Type your tag names separated by a space and hit enter

Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells.
Hypertens Res. 2005 Feb; 28(2):165-72.HR

Abstract

Adrenomedullin (AM), a potent vasodilator peptide, has recently been suggested to function as an endogenous antioxidant. However, its potential site of action at the cellular level has not been clarified. The present study was undertaken to investigate whether AM directly inhibits intracellular reactive oxygen species (ROS) generation and redox-sensitive gene expression stimulated by angiotensin (Ang) II in rat aortic endothelial cells (ECs). Ang II (10(-7) mol/l) significantly increased intracellular ROS levels in ECs as measured by dichlorofluorescein (DCF) fluorescence. AM inhibited Ang II-stimulated ROS generation in a dose-dependent manner and this effect was abolished by a superoxide radical scavenger, NAD(P)H oxidase inhibitor, and a protein kinase A (PKA) inhibitor, and mimicked by a cell-permeable cAMP analog. A real-time reverse transcription-polymerase chain reaction (RT-PCR) study showed that Ang II significantly upregulated a set of redox-sensitive genes (ICAM-1, VCAM-1, PAI-1, tissue factor, MCP-1, osteopontin), and these effects were blocked by an antioxidant, N-acetyl cysteine (NAC). AM similarly and dose-dependently inhibited the Ang II-induced upregulation of the entire set of these genes via a receptor-mediated and PKA-dependent pathway, and the degrees of inhibition were similar to those by NAC. In conclusion, the present study demonstrated that AM potently blocked the Ang II-stimulated intracellular ROS generation from NAD(P)H oxidase and the subsequent redox-sensitive gene expression via a cAMP-dependent mechanism in ECs, suggesting that AM has vasculoprotective effects against pro-oxidant stimuli.

Authors+Show Affiliations

Department of Clinical and Molecular Endocrinology, Tokyo Medical and Dental University Graduate School, Tokyo, Japan. tyoshimoto.cme@tmd.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16025744

Citation

Yoshimoto, Takanobu, et al. "Adrenomedullin Inhibits Angiotensin II-induced Oxidative Stress and Gene Expression in Rat Endothelial Cells." Hypertension Research : Official Journal of the Japanese Society of Hypertension, vol. 28, no. 2, 2005, pp. 165-72.
Yoshimoto T, Gochou N, Fukai N, et al. Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells. Hypertens Res. 2005;28(2):165-72.
Yoshimoto, T., Gochou, N., Fukai, N., Sugiyama, T., Shichiri, M., & Hirata, Y. (2005). Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells. Hypertension Research : Official Journal of the Japanese Society of Hypertension, 28(2), 165-72.
Yoshimoto T, et al. Adrenomedullin Inhibits Angiotensin II-induced Oxidative Stress and Gene Expression in Rat Endothelial Cells. Hypertens Res. 2005;28(2):165-72. PubMed PMID: 16025744.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adrenomedullin inhibits angiotensin II-induced oxidative stress and gene expression in rat endothelial cells. AU - Yoshimoto,Takanobu, AU - Gochou,Naoki, AU - Fukai,Nozomi, AU - Sugiyama,Toru, AU - Shichiri,Masayoshi, AU - Hirata,Yukio, PY - 2005/7/20/pubmed PY - 2005/8/12/medline PY - 2005/7/20/entrez SP - 165 EP - 72 JF - Hypertension research : official journal of the Japanese Society of Hypertension JO - Hypertens Res VL - 28 IS - 2 N2 - Adrenomedullin (AM), a potent vasodilator peptide, has recently been suggested to function as an endogenous antioxidant. However, its potential site of action at the cellular level has not been clarified. The present study was undertaken to investigate whether AM directly inhibits intracellular reactive oxygen species (ROS) generation and redox-sensitive gene expression stimulated by angiotensin (Ang) II in rat aortic endothelial cells (ECs). Ang II (10(-7) mol/l) significantly increased intracellular ROS levels in ECs as measured by dichlorofluorescein (DCF) fluorescence. AM inhibited Ang II-stimulated ROS generation in a dose-dependent manner and this effect was abolished by a superoxide radical scavenger, NAD(P)H oxidase inhibitor, and a protein kinase A (PKA) inhibitor, and mimicked by a cell-permeable cAMP analog. A real-time reverse transcription-polymerase chain reaction (RT-PCR) study showed that Ang II significantly upregulated a set of redox-sensitive genes (ICAM-1, VCAM-1, PAI-1, tissue factor, MCP-1, osteopontin), and these effects were blocked by an antioxidant, N-acetyl cysteine (NAC). AM similarly and dose-dependently inhibited the Ang II-induced upregulation of the entire set of these genes via a receptor-mediated and PKA-dependent pathway, and the degrees of inhibition were similar to those by NAC. In conclusion, the present study demonstrated that AM potently blocked the Ang II-stimulated intracellular ROS generation from NAD(P)H oxidase and the subsequent redox-sensitive gene expression via a cAMP-dependent mechanism in ECs, suggesting that AM has vasculoprotective effects against pro-oxidant stimuli. SN - 0916-9636 UR - https://www.unboundmedicine.com/medline/citation/16025744/Adrenomedullin_inhibits_angiotensin_II_induced_oxidative_stress_and_gene_expression_in_rat_endothelial_cells_ L2 - https://antibodies.cancer.gov/detail/CPTC-SPP1-1 DB - PRIME DP - Unbound Medicine ER -