Hydrogen sulfide attenuates hyperhomocysteinemia-induced cardiomyocytic endoplasmic reticulum stress in rats.
The mechanisms responsible for the cardioprotective effect of hydrogen sulfide (H(2)S) are unclear. The present study was designed to examine whether H(2)S could regulate hyperhomocysteinemia (HHcy)-induced cardiomyocytic endoplasmic reticulum (ER) stress. A rat model of HHcy was produced, and H9c2 cells (rat embryonic heart-derived cell line) were cultured. The plasma homocysteine was measured by using HPLC. Plasma H(2)S concentration and myocardial H(2)S production were measured with a sulfide-sensitive electrode. Confocal immunofluorescent analysis for cardiomyocytic C/EBP homologous protein (CHOP) was performed. Glucose-regulated protein 78 (GRP78), CHOP, and caspase 12 expressions by myocardial tissues and cleaved caspase 12 and p-eIF2alpha expressions by H9c2 cells were detected with Western blotting. The results showed that methionine overload induced HHcy, resulting in a marked cardiomyocytic ER stress, whereas endogenous production of H(2)S was reduced in rats with HHcy. H(2)S supplementation, however, decreased expressions of ER stress-associated proteins, including GRP78, CHOP, and caspase 12, by myocardial tissues in vivo. The inhibition of endogenous H(2)S production further enhanced cardiomyocytic ER stress, but H(2)S supplementation effectively antagonized the H9c2 cell CHOP, cleaved caspase 12 and p-eIF2alpha expressions induced by Hcy, thapsigargin, or tunicamycin in vitro. The results suggest that H(2)S can attenuate cardiomyocytic ER stress in HHcy-induced cardiomyocytic injury.
Wei
Hongling
H
Department of Pediatrics, Peking University First Hospital, Xi-An Men Street No. 1, West District, Beijing, P.R. China.
Zhang
Rongyuan
R
Jin
Hongfang
H
Liu
Die
D
Tang
Xiuying
X
Tang
Chaoshu
C
Du
Junbao
J
D000818:Animals; D053454:Caspase 12 / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000737:chemistry* / Q000378:metabolism; D020138:Hyperhomocysteinemia / Q000188:drug therapy*; D008297:Male; D008715:Methionine / Q000737:chemistry; D046529:Microscopy, Electron, Transmission / Q000379:methods; D032383:Myocytes, Cardiac / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP
D053454:Caspase 12; D006360:Heat-Shock Proteins; D006862:Hydrogen Sulfide; D008715:Methionine; D019284:Thapsigargin; D051742:Transcription Factor CHOP; D014415:Tunicamycin; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP