title: Inhibition of hydrogen sulfide on the proliferation of vascular smooth muscle cells involved in the modulation of calcium sensing receptor in high homocysteine.
abstract: Hyperhomocysteinemia induces the proliferation of vascular smooth muscle cells (VSMCs). Hydrogen sulfide (H2S) inhibits the phenotype switch of VSMCs and calcium-sensing receptor (CaSR) regulated the production of endogenous H2S. However, whether CaSR inhibits the proliferation of VSMCs by regulating the endogenous cystathionine-gamma-lyase (CSE, a major enzyme that produces H2S) pathway in high homocysteine (HHcy) has not been previously investigated. The intracellular calcium concentration, the concentration of H2S, the cell viability, the proliferation and the expression of proteins of cultured VSMCs from rat thoracic aortas were measured, respectively. The results showed that the [Ca(2+)]i and the expression of p-CaMK and CSE increased upon treatment with CaSR agonist. In HHcy, the H2S concentration decrease, the proliferation and migration rate increased, the expression of Cyclin D1, PCNA, Osteopontin and p-Erk1/2 increased while the α-SM actin, P21(Cip/WAK-1) and Calponin decreased. The CaSR agonist or exogenous H2S significantly reversed the changes of VSMCs caused by HHcy. In conclusion, our results demonstrated that CaSR regulate the endogenous CSE/H2S is related to the PLC-IP3 receptor and CaM signal pathways which inhibit the proliferation of VSMCs, and the latter is involved in the Erk1/2 dependent signal pathway in high homocysteine.
authors: Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors: Yuwen
authors: Y
authors: Wang
authors: Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors: Xiyao
authors: X
authors: Wang
authors: Department of Radiology, Central Hospital of the Red Cross, Harbin 150080, China.
authors: Xiaohui
authors: X
authors: Liang
authors: Department of Pathophysiology, Harbin Medical University, Harbin 150081, China.
authors: Jichao
authors: J
authors: Wu
authors: Department of Pathophysiology, Harbin Medical University, Harbin 150081, China.
authors: Shiyun
authors: S
authors: Dong
authors: Department of Pathophysiology, Harbin Medical University, Harbin 150081, China.
authors: Hongzhu
authors: H
authors: Li
authors: Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081, China.
authors: Meili
authors: M
authors: Jin
authors: Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150086, China.
authors: Dianjun
authors: D
authors: Sun
authors: Department of Pathophysiology, Harbin Medical University, Harbin 150081, China.
authors: Weihua
authors: W
authors: Zhang
authors: Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. Electronic address: xzhong1111@163.com.
authors: Xin
authors: X
authors: Zhong
mesh_terms: D000293:Adolescent; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: C506457:(R)-2-(1-(1-naphthyl)ethyl-aminom-ethyl)indole; D002147:Calmodulin; D007211:Indoles; D009281:Naphthalenes; D044169:Receptors, Calcium-Sensing; D006710:Homocysteine; D015544:Inositol 1,4,5-Trisphosphate; D010738:Type C Phospholipases; D003542:Cystathionine gamma-Lyase; D001973:Bromodeoxyuridine; D002118:Calcium; D006862:Hydrogen Sulfide
keywords: Calcium sensing receptor; High homocysteine; Hydrogen sulfide; Smooth muscle cells