Abstract
Hydrogen sulfide (H2S) has been shown to protect against oxidative stress injury and inflammation in various hypoxia-induced insult models. However, it remains unknown whether H2S protects human skin keratinocytes (HaCaT cells) against chemical hypoxia-induced damage. In the current study, HaCaT cells were treated with cobalt chloride (CoCl2), a well known hypoxia mimetic agent, to establish a chemical hypoxia-induced cell injury model. Our findings showed that pretreatment of HaCaT cells with NaHS (a donor of H2S) for 30 min before exposure to CoCl2 for 24 h significantly attenuated CoCl2-induced injuries and inflammatory responses, evidenced by increases in cell viability and GSH level and decreases in ROS generation and secretions of IL-1β, IL-6 and IL-8. In addition, pretreatment with NaHS markedly reduced CoCl2-induced COX-2 overexpression and PGE2 secretion as well as intranuclear NF-κB p65 subunit accumulation (the central step of NF-κB activation). Similar to the protective effect of H2S, both NS-398 (a selective COX-2 inhibitor) and PDTC (a selective NF-κB inhibitor) depressed not only CoCl2-induced cytotoxicity, but also the secretions of IL-1β, IL-6 and IL-8. Importantly, PDTC obviously attenuated overexpression of COX-2 induced by CoCl2. Notably, NAC, a ROS scavenger, conferred a similar protective effect of H2S against CoCl2-induced insults and inflammatory responses. Taken together, the findings of the present study have demonstrated for the first time that H2S protects HaCaT cells against CoCl2-induced injuries and inflammatory responses through inhibition of ROS-activated NF-κB/COX-2 pathway.
Highlights
Hydrogen sulfide (H2S), an endogenous gaseous mediator, is produced by pyridoxal-59-phosphate-dependent enzymes, including cystathionine-c-lyase (CGL, CSE), cystathionine-b-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), during cysteine metabolism [1,2]
H2S inhibits CoCl2-induced cytotoxicity in HaCaT cells To investigate the effect of H2S on CoCl2-induced cytotoxicity, cell viability was detected by Cell Counter Kit-8 (CCK-8) assay
The results indicate that H2S pretreatment protects against CoCl2-induced toxicity in HaCaT cells
Summary
Hydrogen sulfide (H2S), an endogenous gaseous mediator, is produced by pyridoxal-59-phosphate-dependent enzymes, including cystathionine-c-lyase (CGL, CSE), cystathionine-b-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), during cysteine metabolism [1,2]. Along with nitric oxide (NO) and carbon monoxide (CO), H2S is considered as the third signaling gasotransmitter, which plays important physiological and physiopathological roles both in vivo and in vitro [3,4]. Accumulating evidence suggests that H2S exerts protective effects against various stimuli-triggered injuries in many organs including heart, liver and kidney [5,6,7]. One of the most important mechanisms responsible for H2S protection is antioxidation, which exerts its effect by increasing reduced glutathione (GSH) in neurons [8], and by directly scavenging superoxide anions, hydrogen peroxide (H2O2) [9] and peroxynitrite [10] to suppress oxidative stress. H2S provokes an inflammatory response via the extracellular signal-regulated kinase (ERK) pathway [12]. The role of H2S in hypoxia-caused dermatic injury has not been reported
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