Endothelin-1 Downregulates Sulfur Dioxide/Aspartate Aminotransferase Pathway Via Reactive Oxygen Species to Promote the Proliferation and Migration of Vascular Smooth Muscle Cells

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2020 Feb 25

PMID 32089786

Citations 8

Authors

Xiaoyu Tian

Qingyou Zhang

Yaqian Huang

Selena Chen

Chaoshu Tang

Yan Sun

Junbao Du

Hongfang Jin

Affiliations

Soon will be listed here.

Abstract

The regulatory mechanisms for proliferation and migration of vascular smooth muscle cells have not yet been clear. The present study was designed to investigate whether and how endothelin-1 (ET-1) impacted the generation of endogenous sulfur dioxide (SO) in rat vascular smooth muscle cell (VSMC) proliferation and migration. Primary VSMCs and purified aspartate aminotransferase (AAT) protein were used in this study. We found that in the presence of ET-1, the expression of PCNA and Ki-67 was upregulated and the migration of VSMCs was promoted, while the AAT activity and SO levels in VSMCs were reduced without any changes in AAT1 and AAT2 expression. SO supplementation successfully prevented the ET-1-facilitated expression of PCNA and Ki-67 and the migration of VSMCs. Interestingly, ET-1 significantly increased reactive oxygen species (ROS) production in association with SO/AAT pathway downregulation in VSMCs compared with controls, while the ROS scavenger N-acetyl-L-cysteine (NAC) and the antioxidant glutathione (GSH) significantly abolished the ET-1-stimulated downregulation of the SO/AAT pathway. Moreover, the AAT activity was reduced in purified protein after the treatment for 2 h. However, NAC and GSH blocked the hydrogen peroxide-induced AAT activity reduction. In conclusion, our results suggest that ET-1 results in the downregulation of the endogenous SO/AAT pathway via ROS generation to enhance the proliferation and migration of VSMCs.

Citing Articles

Interdialytic home systolic blood pressure variability increases all-cause mortality in hemodialysis patients.

Dong L, Tian M, Li H, Dong J, Song X Clin Cardiol. 2024; 47(4):e24259.

PMID: 38549547 PMC: 10979187. DOI: 10.1002/clc.24259.

Changes in glutamic oxaloacetic transaminase 2 during rat physiological and pathological cardiomyocyte hypertrophy.

Liu X, Li X, Zhou H BMC Cardiovasc Disord. 2023; 23(1):595.

PMID: 38053021 PMC: 10696840. DOI: 10.1186/s12872-023-03648-3.

Advances in the research of sulfur dioxide and pulmonary hypertension.

Liu X, Zhou H, Zhang H, Jin H, He Y Front Pharmacol. 2023; 14:1282403.

PMID: 37900169 PMC: 10602757. DOI: 10.3389/fphar.2023.1282403.

Role of ryanodine receptor 2 and FK506-binding protein 12.6 dissociation in pulmonary hypertension.

Wang Y, Reyes-Garcia J, Di Mise A, Zheng Y J Gen Physiol. 2023; 155(3.

PMID: 36625865 PMC: 9836826. DOI: 10.1085/jgp.202213100.

Role of advanced glycation end products on vascular smooth muscle cells under diabetic atherosclerosis.

Mao L, Yin R, Yang L, Zhao D Front Endocrinol (Lausanne). 2022; 13:983723.

PMID: 36120471 PMC: 9470882. DOI: 10.3389/fendo.2022.983723.

References

Li M, Mian M, Barhoumi T, Rehman A, Mann K, Paradis P . Endothelin-1 overexpression exacerbates atherosclerosis and induces aortic aneurysms in apolipoprotein E knockout mice. Arterioscler Thromb Vasc Biol. 2013; 33(10):2306-15. DOI: 10.1161/ATVBAHA.113.302028. View

Wedgwood S, Black S . Endothelin-1 decreases endothelial NOS expression and activity through ETA receptor-mediated generation of hydrogen peroxide. Am J Physiol Lung Cell Mol Physiol. 2004; 288(3):L480-7. DOI: 10.1152/ajplung.00283.2004. View

Shuang T, Fu M, Yang G, Wu L, Wang R . The interaction of IGF-1/IGF-1R and hydrogen sulfide on the proliferation of mouse primary vascular smooth muscle cells. Biochem Pharmacol. 2017; 149:143-152. DOI: 10.1016/j.bcp.2017.12.009. View

Fei J, Viedt C, Soto U, Elsing C, Jahn L, Kreuzer J . Endothelin-1 and smooth muscle cells: induction of jun amino-terminal kinase through an oxygen radical-sensitive mechanism. Arterioscler Thromb Vasc Biol. 2000; 20(5):1244-9. DOI: 10.1161/01.atv.20.5.1244. View

Bou Daou G, Srivastava A . Reactive oxygen species mediate Endothelin-1-induced activation of ERK1/2, PKB, and Pyk2 signaling, as well as protein synthesis, in vascular smooth muscle cells. Free Radic Biol Med. 2004; 37(2):208-15. DOI: 10.1016/j.freeradbiomed.2004.04.018. View

Brennan L, Steinhorn R, Wedgwood S, Mata-Greenwood E, Roark E, Russell J . Increased superoxide generation is associated with pulmonary hypertension in fetal lambs: a role for NADPH oxidase. Circ Res. 2003; 92(6):683-91. DOI: 10.1161/01.RES.0000063424.28903.BB. View

Sun Y, Tian Y, Prabha M, Liu D, Chen S, Zhang R . Effects of sulfur dioxide on hypoxic pulmonary vascular structural remodeling. Lab Invest. 2009; 90(1):68-82. DOI: 10.1038/labinvest.2009.102. View

Liu S, Brook R, Huang W, Fan Z, Xu H, Wu R . Extreme levels of ambient air pollution adversely impact cardiac and central aortic hemodynamics: the AIRCMD-China study. J Am Soc Hypertens. 2017; 11(11):754-761.e3. DOI: 10.1016/j.jash.2017.09.009. View

Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y . A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988; 332(6163):411-5. DOI: 10.1038/332411a0. View

10.

Babior B . Phagocytes and oxidative stress. Am J Med. 2000; 109(1):33-44. DOI: 10.1016/s0002-9343(00)00481-2. View

11.

McCord J . The evolution of free radicals and oxidative stress. Am J Med. 2000; 108(8):652-9. DOI: 10.1016/s0002-9343(00)00412-5. View

12.

Zhao X, Jin H, Tang C, Du J . [Effect of sulfur dioxide on vascular collagen remodeling in spontaneously hypertensive rats]. Zhonghua Er Ke Za Zhi. 2009; 46(12):905-8. View

13.

Montezano A, Burger D, Paravicini T, Chignalia A, Yusuf H, Almasri M . Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 (Nox5) regulation by angiotensin II and endothelin-1 is mediated via calcium/calmodulin-dependent, rac-1-independent pathways in human endothelial cells. Circ Res. 2010; 106(8):1363-73. PMC: 3119893. DOI: 10.1161/CIRCRESAHA.109.216036. View

14.

Levonen A, Vahakangas E, Koponen J, Yla-Herttuala S . Antioxidant gene therapy for cardiovascular disease: current status and future perspectives. Circulation. 2008; 117(16):2142-50. DOI: 10.1161/CIRCULATIONAHA.107.718585. View

15.

Chen S, Tang C, Jin H, Du J . Sulfur dioxide acts as a novel endogenous gaseous signaling molecule in the cardiovascular system. Chin Med J (Engl). 2011; 124(12):1901-5. View

16.

Yoshizumi M, Kim S, Kagami S, Hamaguchi A, Tsuchiya K, Houchi H . Effect of endothelin-1 (1-31) on extracellular signal-regulated kinase and proliferation of human coronary artery smooth muscle cells. Br J Pharmacol. 1998; 125(5):1019-27. PMC: 1565664. DOI: 10.1038/sj.bjp.0702141. View

17.

Viel E, Benkirane K, Javeshghani D, Touyz R, Schiffrin E . Xanthine oxidase and mitochondria contribute to vascular superoxide anion generation in DOCA-salt hypertensive rats. Am J Physiol Heart Circ Physiol. 2008; 295(1):H281-8. PMC: 2494748. DOI: 10.1152/ajpheart.00304.2008. View

18.

Sun A, Wang Y, Liu J, Yu X, Sun Y, Yang F . Exogenous H2S modulates mitochondrial fusion-fission to inhibit vascular smooth muscle cell proliferation in a hyperglycemic state. Cell Biosci. 2016; 6:36. PMC: 4888644. DOI: 10.1186/s13578-016-0102-x. View

19.

Griendling K, Sorescu D, Ushio-Fukai M . NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res. 2000; 86(5):494-501. DOI: 10.1161/01.res.86.5.494. View

20.

Chen C, Cheng T, Lin H, Shih N, Chen Y, Chen Y . Reactive oxygen species generation is involved in epidermal growth factor receptor transactivation through the transient oxidization of Src homology 2-containing tyrosine phosphatase in endothelin-1 signaling pathway in rat cardiac fibroblasts. Mol Pharmacol. 2006; 69(4):1347-55. DOI: 10.1124/mol.105.017558. View