Oxidative stress induced by homocysteine <i>via</i> activating JNK signaling pathway in vascular smooth muscle cells

SHEN Qirui; LI Yonghua; ZHANG Wenjie; WANG Pei

doi:10.3969/j.issn.1006-0111.2018.06.005

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Volume 36 Issue 6

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Article Navigation > Journal of Pharmaceutical Practice and Service > 2018 > 36(6): 499-502,511

SHEN Qirui, LI Yonghua, ZHANG Wenjie, WANG Pei. Oxidative stress induced by homocysteine via activating JNK signaling pathway in vascular smooth muscle cells[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(6): 499-502,511. doi: 10.3969/j.issn.1006-0111.2018.06.005

Citation:

SHEN Qirui, LI Yonghua, ZHANG Wenjie, WANG Pei. Oxidative stress induced by homocysteine via activating JNK signaling pathway in vascular smooth muscle cells[J]. Journal of Pharmaceutical Practice and Service, 2018, 36(6): 499-502,511. doi: 10.3969/j.issn.1006-0111.2018.06.005

Oxidative stress induced by homocysteine via activating JNK signaling pathway in vascular smooth muscle cells

doi: 10.3969/j.issn.1006-0111.2018.06.005

1.
School of Life Sciences, China Jiliang University, Hangzhou 310018, China
2.
Department of Anesthesiology, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai 200003, China
3.
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2018-04-28
Rev Recd Date: 2018-06-01

Abstract

Objective To investigate the influence and the underlying mechanisms of homocysteine on oxidative stress production in vascular smooth muscle cells (VSMC). Methods A10 cell line (a kind of VSMC) was cultured in vitro. Three different concentrations of homocysteine (5, 30 and 100 μmol/L) were added into the medium for 48 hours and then cells were lysed for determination of reactive oxygen species (ROS) production, H₂O₂ level and total anti-oxidant capacity. Moreover, the effects of homocysteine on JNK signaling pathway were evaluated by immunoblotting. Results ROS production (P<0.05) in VSMC were induced by three different concentrations of homocysteine (5, 30 and 100 μmol/L). Two concentrations of homocysteine (30 and 100 μmol/L) increased H₂O₂ content and decreased T-AOC. Moreover, homocysteine induced phosphorylation of JNK in VSMC in a dose-dependent manner (P<0.05). Conclusion Oxidative stress induced by homocysteine via activating JNK signaling pathway in VSMC.
- oxidative stress,
- homocysteine,
- vascular smooth muscle cells,
- JNK

References

[1]	NYGARD O, VOLLSET SE, REFSUM H, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study[J]. JAMA,1995,274(19):1526-1533.
[2]	LI Z, SUN L, ZHANG H, et al. Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke:a multicenter case-control study in China[J]. Stroke,2003,34(9):2085-2090.
[3]	YE Z, WANG C, ZHANG Q, et al. Prevalence of homocysteine-related hypertension in patients with chronic kidney disease[J]. J Clin Hypertens (Greenwich),2017,19(2):151-160.
[4]	HAN L, WU Q, WANG C, et al. Homocysteine, ischemic stroke, and coronary heart disease in hypertensive patients:a population-based, prospective cohort study[J]. Stroke,2015,46(7):1777-1786.
[5]	RODRIGO R, PASSALACQUA W, ARAYA J, et al. Implications of oxidative stress and homocysteine in the pathophysiology of essential hypertension[J]. J Cardiovasc Pharmacol,2003,42(4):453-461.
[6]	XI H, ZHANG Y, XU Y, et al. Caspase-1 inflammasome activation mediates homocysteine-induced pyrop-apoptosis in endothelial cells[J]. Circ Res,2016,118(10):1525-1539.
[7]	CHANG PY, LU SC, LEE CM, et al. Homocysteine inhibits arterial endothelial cell growth through transcriptional downregulation of fibroblast growth factor-2 involving G protein and DNA methylation[J]. Circ Res,2008,102(8):933-941.
[8]	ZHANG D, XIE X, CHEN Y, et al. Homocysteine upregulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo[J]. Circ Res,2012,110(6):808-817.
[9]	MUJUMDAR VS, HAYDEN MR, TYAGI SC. Homocyst(e)ine induces calcium second messenger in vascular smooth muscle cells[J]. J Cell Physiol,2000,183(1):28-36.
[10]	ZHANG D, CHEN Y, XIE X, et al. Homocysteine activates vascular smooth muscle cells by DNA demethylation of platelet-derived growth factor in endothelial cells[J]. J Mol Cell Cardiol,2012,53(4):487-496.
[11]	ZOU T, YANG W, HOU Z, et al. Homocysteine enhances cell proliferation in vascular smooth muscle cells:role of p38 MAPK and p47phox[J]. Acta Biochim Biophys Sin (Shanghai),2010,42(12):908-915.
[12]	TSAI JC, WANG H, PERRELLA MA, et al. Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells[J]. J Clin Invest,1996,97(1):146-153.
[13]	TSAI JC, PERRELLA MA, YOSHIZUMI M, et al. Promotion of vascular smooth muscle cell growth by homocysteine:a link to atherosclerosis[J]. Proc Natl Acad Sci USA,1994,91(14):6369-6373.
[14]	DALTON ML, GADSON PF, WRENN RW, et al. Homocysteine signal cascade:production of phospholipids, activation of protein kinase C, and the induction of c-fos and c-myb in smooth muscle cells[J]. FASEB J,1997,11(8):703-711.
[15]	BROWN JC, ROSENQUIST TH, MONAGHAn DT. ERK2 activation by homocysteine in vascular smooth muscle cells[J]. Biochem Biophys Res Commun,1998,251(3):669-676.
[16]	DORONZO G, RUSSO I, MATTIELLO L, et al. Homocysteine rapidly increases matrix metalloproteinase-2 expression and activity in cultured human vascular smooth muscle cells. Role of phosphatidyl inositol 3-kinase and mitogen activated protein kinase pathways[J]. Thromb Haemost,,2005,94(6):1285-1293.
[17]	CHANG L, XU JX, ZHAO J, et al. Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells[J]. Acta Pharmacol Sin,,2004,25(3):341-346.
[18]	SHIRPOOR A, SALAMI S, KHADEM ANSARI MH, et al. Ethanol promotes rat aortic vascular smooth muscle cell proliferation via increase of homocysteine and oxidized-low-density lipoprotein[J]. J Cardiol,2013,62(6):374-378.
[19]	LUO X, XIAO Y, SONG F, et al. Increased plasma S-adenosyl-homocysteine levels induce the proliferation and migration of VSMCs through an oxidative stress-ERK1/2 pathway in apoE(-/-) mice[J]. Cardiovasc Res,2012,95(2):241-250.
[20]	ZHANG L, ZHOU M, WANG Y, et al. miR-92a inhibits vascular smooth muscle cell apoptosis:role of the MKK4-JNK pathway[J]. Apoptosis,2014,19(6):975-983.
[21]	LIU YZ, CHEN JK, LI ZP, et al. High-salt diet enhances hippocampal oxidative stress and cognitive impairment in mice[J]. Neurobiol Learn Mem,2014,114:10-15.
[22]	ZHANG XJ, HE C, TIAN K, et al. Ginsenoside Rb1 attenuates angiotensin Ⅱ-induced abdominal aortic aneurysm through inactivation of the JNK and p38 signaling pathways[J]. Vascul Pharmacol,2015,73:86-95.
[23]	CHENG Y, QIU F, TASHIRO S, et al. ERK and JNK mediate TNFalpha-induced p53 activation in apoptotic and autophagic L929 cell death[J]. Biochem Biophys Res Commun,2008,376(3):483-488.
[24]	SHEN HM, LIU ZG. JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species[J]. Free Radic Biol Med,2006,40(6):928-939.

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通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

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Oxidative stress induced by homocysteine via activating JNK signaling pathway in vascular smooth muscle cells

1. School of Life Sciences, China Jiliang University, Hangzhou 310018, China

2. Department of Anesthesiology, Changzheng Hospital Affiliated to Second Military Medical University, Shanghai 200003, China

3. Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

Received Date: 2018-04-28

Rev Recd Date: 2018-06-01

Key words:

Abstract: Objective To investigate the influence and the underlying mechanisms of homocysteine on oxidative stress production in vascular smooth muscle cells (VSMC). Methods A10 cell line (a kind of VSMC) was cultured in vitro. Three different concentrations of homocysteine (5, 30 and 100 μmol/L) were added into the medium for 48 hours and then cells were lysed for determination of reactive oxygen species (ROS) production, H₂O₂ level and total anti-oxidant capacity. Moreover, the effects of homocysteine on JNK signaling pathway were evaluated by immunoblotting. Results ROS production (P<0.05) in VSMC were induced by three different concentrations of homocysteine (5, 30 and 100 μmol/L). Two concentrations of homocysteine (30 and 100 μmol/L) increased H₂O₂ content and decreased T-AOC. Moreover, homocysteine induced phosphorylation of JNK in VSMC in a dose-dependent manner (P<0.05). Conclusion Oxidative stress induced by homocysteine via activating JNK signaling pathway in VSMC.

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Reference (24)

[1]	NYGARD O, VOLLSET SE, REFSUM H, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study[J]. JAMA,1995,274(19):1526-1533.
[2]	LI Z, SUN L, ZHANG H, et al. Elevated plasma homocysteine was associated with hemorrhagic and ischemic stroke, but methylenetetrahydrofolate reductase gene C677T polymorphism was a risk factor for thrombotic stroke:a multicenter case-control study in China[J]. Stroke,2003,34(9):2085-2090.
[3]	YE Z, WANG C, ZHANG Q, et al. Prevalence of homocysteine-related hypertension in patients with chronic kidney disease[J]. J Clin Hypertens (Greenwich),2017,19(2):151-160.
[4]	HAN L, WU Q, WANG C, et al. Homocysteine, ischemic stroke, and coronary heart disease in hypertensive patients:a population-based, prospective cohort study[J]. Stroke,2015,46(7):1777-1786.
[5]	RODRIGO R, PASSALACQUA W, ARAYA J, et al. Implications of oxidative stress and homocysteine in the pathophysiology of essential hypertension[J]. J Cardiovasc Pharmacol,2003,42(4):453-461.
[6]	XI H, ZHANG Y, XU Y, et al. Caspase-1 inflammasome activation mediates homocysteine-induced pyrop-apoptosis in endothelial cells[J]. Circ Res,2016,118(10):1525-1539.
[7]	CHANG PY, LU SC, LEE CM, et al. Homocysteine inhibits arterial endothelial cell growth through transcriptional downregulation of fibroblast growth factor-2 involving G protein and DNA methylation[J]. Circ Res,2008,102(8):933-941.
[8]	ZHANG D, XIE X, CHEN Y, et al. Homocysteine upregulates soluble epoxide hydrolase in vascular endothelium in vitro and in vivo[J]. Circ Res,2012,110(6):808-817.
[9]	MUJUMDAR VS, HAYDEN MR, TYAGI SC. Homocyst(e)ine induces calcium second messenger in vascular smooth muscle cells[J]. J Cell Physiol,2000,183(1):28-36.
[10]	ZHANG D, CHEN Y, XIE X, et al. Homocysteine activates vascular smooth muscle cells by DNA demethylation of platelet-derived growth factor in endothelial cells[J]. J Mol Cell Cardiol,2012,53(4):487-496.
[11]	ZOU T, YANG W, HOU Z, et al. Homocysteine enhances cell proliferation in vascular smooth muscle cells:role of p38 MAPK and p47phox[J]. Acta Biochim Biophys Sin (Shanghai),2010,42(12):908-915.
[12]	TSAI JC, WANG H, PERRELLA MA, et al. Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells[J]. J Clin Invest,1996,97(1):146-153.
[13]	TSAI JC, PERRELLA MA, YOSHIZUMI M, et al. Promotion of vascular smooth muscle cell growth by homocysteine:a link to atherosclerosis[J]. Proc Natl Acad Sci USA,1994,91(14):6369-6373.
[14]	DALTON ML, GADSON PF, WRENN RW, et al. Homocysteine signal cascade:production of phospholipids, activation of protein kinase C, and the induction of c-fos and c-myb in smooth muscle cells[J]. FASEB J,1997,11(8):703-711.
[15]	BROWN JC, ROSENQUIST TH, MONAGHAn DT. ERK2 activation by homocysteine in vascular smooth muscle cells[J]. Biochem Biophys Res Commun,1998,251(3):669-676.
[16]	DORONZO G, RUSSO I, MATTIELLO L, et al. Homocysteine rapidly increases matrix metalloproteinase-2 expression and activity in cultured human vascular smooth muscle cells. Role of phosphatidyl inositol 3-kinase and mitogen activated protein kinase pathways[J]. Thromb Haemost,,2005,94(6):1285-1293.
[17]	CHANG L, XU JX, ZHAO J, et al. Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells[J]. Acta Pharmacol Sin,,2004,25(3):341-346.
[18]	SHIRPOOR A, SALAMI S, KHADEM ANSARI MH, et al. Ethanol promotes rat aortic vascular smooth muscle cell proliferation via increase of homocysteine and oxidized-low-density lipoprotein[J]. J Cardiol,2013,62(6):374-378.
[19]	LUO X, XIAO Y, SONG F, et al. Increased plasma S-adenosyl-homocysteine levels induce the proliferation and migration of VSMCs through an oxidative stress-ERK1/2 pathway in apoE(-/-) mice[J]. Cardiovasc Res,2012,95(2):241-250.
[20]	ZHANG L, ZHOU M, WANG Y, et al. miR-92a inhibits vascular smooth muscle cell apoptosis:role of the MKK4-JNK pathway[J]. Apoptosis,2014,19(6):975-983.
[21]	LIU YZ, CHEN JK, LI ZP, et al. High-salt diet enhances hippocampal oxidative stress and cognitive impairment in mice[J]. Neurobiol Learn Mem,2014,114:10-15.
[22]	ZHANG XJ, HE C, TIAN K, et al. Ginsenoside Rb1 attenuates angiotensin Ⅱ-induced abdominal aortic aneurysm through inactivation of the JNK and p38 signaling pathways[J]. Vascul Pharmacol,2015,73:86-95.
[23]	CHENG Y, QIU F, TASHIRO S, et al. ERK and JNK mediate TNFalpha-induced p53 activation in apoptotic and autophagic L929 cell death[J]. Biochem Biophys Res Commun,2008,376(3):483-488.
[24]	SHEN HM, LIU ZG. JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species[J]. Free Radic Biol Med,2006,40(6):928-939.

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Oxidative stress induced by homocysteine via activating JNK signaling pathway in vascular smooth muscle cells

doi: 10.3969/j.issn.1006-0111.2018.06.005

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References

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Oxidative stress induced by homocysteine via activating JNK signaling pathway in vascular smooth muscle cells

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Oxidative stress induced by homocysteine via activating JNK signaling pathway in vascular smooth muscle cells

doi: 10.3969/j.issn.1006-0111.2018.06.005

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References

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Oxidative stress induced by homocysteine via activating JNK signaling pathway in vascular smooth muscle cells

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