H₂S Protects Against Methionine–Induced Oxidative Stress in Brain Endothelial Cells

Abstract

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 H 2 S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H 2 S 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 H 2 S). 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), N -nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H 2 S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H 2 S may have therapeutic potential against Met-induced oxidative stress. Antioxid. Redox Signal. 11,[25][26][27][28][29][30][31][32][33]

S-Glutathionylation Enhances Human Cystathionine β-Synthase Activity Under Oxidative Stress Conditions

“…In tissues such as the brain, where CBS is dominant, enhanced H 2 S production might be a significant outcome of oxidative stress-induced glutathionylation. H 2 S has been shown to protect against oxidative stress in brain cells (25,52) and in HUVECs (55).…”

Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising

“…Inhibition of 'oxidative stress' by inactivating enzymes or the direct 'scavenging' of the oxidant species would be expected to contribute to the many potential anti-inflammatory effects of H 2 S. In vitro experiments have shown that H 2 S generated from sulfide salts (Na 2 S and NaSH) inhibits cellular damage and intracellular protein oxidation induced by HOCl [77,78], ONOO - [79] and • NO [34,80]. NaSH is also reported to scavenge and/or degrade lipid peroxides [81,82] and inhibit the expression and activity of NAD(P)H oxidase [83,84]. Increased hepatic glutathione (GSH) synthesis and decreased lipid peroxidation are also observed with Na 2 S treatment in a murine hepatic ischemia-reperfusion injury model [85].…”

Role of MicroRNA29b in Blood–Brain Barrier Dysfunction during Hyperhomocysteinemia: An Epigenetic Mechanism

“…24 Briefly, cells were incubated with the dye for 20 minutes at 371C, washed with phosphate-buffered saline, and analyzed through laser scanning confocal microscope (  60, and  100 objective, FluoView 1000; Olympus, Center Valley, PA, USA). For flow cytometry, the cells were scrapped and subjected to Accuri's C6 Flow Cytometer (Accuri Cytometers, Ann Harbor, MI, USA).…”