H2S protects against methionine-induced oxidative stress in brain endothelial cells.
Homocysteine (Hcy) causes cerebrovascular dysfunction by inducing oxidative stress. However, to date, there are no strategies to prevent Hcy-induced oxidative damage. Hcy is an H2S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H2S ameliorated Met-induced oxidative stress in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to Met treatment in the presence or absence of NaHS (donor of H2S). Met-induced cell toxicity increased the levels of free radicals in a concentration-dependent manner. Met increased NADPH-oxidase-4 (NOX-4) expression and mitigated thioredxion-1(Trx-1) expression. Pretreatment of bEnd3 with NaHS (0.05 mM) attenuated the production of free radicals in the presence of Met and protected the cells from oxidative damage. Furthermore, NaHS enhanced inhibitory effects of apocynin, N-acetyl-l-cysteine (NAC), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Nomega-nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress.
Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA. suresh.tyagi@louisville.edu
Neetu
N
Tyagi
Karni S
KS
Moshal
Utpal
U
Sen
Thomas P
TP
Vacek
Munish
M
Kumar
William M
WM
Hughes
Soumi
S
Kundu
Suresh C
SC
Tyagi
D000098:Acetophenones / Q000378:metabolism; D000111:Acetylcysteine / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000166:cytology*; D002374:Catalase / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005562:Formazans / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006710:Homocysteine / Q000096:biosynthesis; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008715:Methionine / Q000633:toxicity*; D051379:Mice; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors
D000098:Acetophenones; D005562:Formazans; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D006710:Homocysteine; C079782:MTT formazan; D008715:Methionine; C056165:acetovanillone; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine; D006862:Hydrogen Sulfide