PMID- 27502588 OWN - NLM STAT- MEDLINE DCOM- 20170515 LR - 20201024 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 347 IP - 1 DP - 2016 Sep 10 TI - Inhibition of hydrogen sulfide on the proliferation of vascular smooth muscle cells involved in the modulation of calcium sensing receptor in high homocysteine. PG - 184-191 LID - S0014-4827(16)30234-8 [pii] LID - 10.1016/j.yexcr.2016.08.004 [doi] AB - 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 alpha-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. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Wang, Yuwen AU - Wang Y AD - Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081, China. FAU - Wang, Xiyao AU - Wang X AD - Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081, China. FAU - Liang, Xiaohui AU - Liang X AD - Department of Radiology, Central Hospital of the Red Cross, Harbin 150080, China. FAU - Wu, Jichao AU - Wu J AD - Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. FAU - Dong, Shiyun AU - Dong S AD - Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. FAU - Li, Hongzhu AU - Li H AD - Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. FAU - Jin, Meili AU - Jin M AD - Department of Clinical Laboratory, The second Affiliated Hospital of Harbin Medical University, Harbin 150081, China. FAU - Sun, Dianjun AU - Sun D AD - Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin 150086, China. FAU - Zhang, Weihua AU - Zhang W AD - Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. FAU - Zhong, Xin AU - Zhong X AD - Department of Pathophysiology, Harbin Medical University, Harbin 150081, China. Electronic address: xzhong1111@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160805 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 ((R)-2-(1-(1-naphthyl)ethyl-aminom-ethyl)indole) RN - 0 (Calmodulin) RN - 0 (Indoles) RN - 0 (Naphthalenes) RN - 0 (Receptors, Calcium-Sensing) RN - 0LVT1QZ0BA (Homocysteine) RN - 85166-31-0 (Inositol 1,4,5-Trisphosphate) RN - EC 3.1.4.- (Type C Phospholipases) RN - EC 4.4.1.1 (Cystathionine gamma-Lyase) RN - G34N38R2N1 (Bromodeoxyuridine) RN - SY7Q814VUP (Calcium) RN - YY9FVM7NSN (Hydrogen Sulfide) SB - IM MH - Adolescent MH - Animals MH - Bromodeoxyuridine/metabolism MH - Calcium/metabolism MH - Calmodulin/metabolism MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Cystathionine gamma-Lyase/metabolism MH - Homocysteine/*pharmacology MH - Humans MH - Hydrogen Sulfide/*pharmacology MH - Indoles/pharmacology MH - Inositol 1,4,5-Trisphosphate/metabolism MH - MAP Kinase Signaling System/drug effects MH - Muscle, Smooth, Vascular/*cytology MH - Myocytes, Smooth Muscle/drug effects/*metabolism MH - Naphthalenes/pharmacology MH - Phenotype MH - Rats MH - Receptors, Calcium-Sensing/*metabolism MH - Signal Transduction/drug effects MH - Type C Phospholipases/metabolism OTO - NOTNLM OT - Calcium sensing receptor OT - High homocysteine OT - Hydrogen sulfide OT - Smooth muscle cells EDAT- 2016/08/10 06:00 MHDA- 2017/05/16 06:00 CRDT- 2016/08/10 06:00 PHST- 2016/06/04 00:00 [received] PHST- 2016/08/01 00:00 [revised] PHST- 2016/08/04 00:00 [accepted] PHST- 2016/08/10 06:00 [entrez] PHST- 2016/08/10 06:00 [pubmed] PHST- 2017/05/16 06:00 [medline] AID - S0014-4827(16)30234-8 [pii] AID - 10.1016/j.yexcr.2016.08.004 [doi] PST - ppublish SO - Exp Cell Res. 2016 Sep 10;347(1):184-191. doi: 10.1016/j.yexcr.2016.08.004. Epub 2016 Aug 5.