Articles: hydrogen-sulfide-metabolism.
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Biochem. Biophys. Res. Commun. · Feb 2014
Endogenous and exogenous hydrogen sulfide facilitates T-type calcium channel currents in Cav3.2-expressing HEK293 cells.
Hydrogen sulfide (H2S), a gasotransmitter, is formed from l-cysteine by multiple enzymes including cystathionine-γ-lyase (CSE). We have shown that an H2S donor, NaHS, causes hyperalgesia in rodents, an effect inhibited by knockdown of Cav3.2 T-type Ca(2+) channels (T-channels), and that NaHS facilitates T-channel-dependent currents (T-currents) in NG108-15 cells that naturally express Cav3.2. In the present study, we asked if endogenous and exogenous H2S participates in regulation of the channel functions in Cav3.2-transfected HEK293 (Cav3.2-HEK293) cells. dl-Propargylglycine (PPG), a CSE inhibitor, significantly decreased T-currents in Cav3.2-HEK293 cells, but not in NG108-15 cells. ⋯ The in vivo potency of Na2S was higher than NaHS. These results suggest that the function of Cav3.2 T-channels is tonically enhanced by endogenous H2S synthesized by CSE in Cav3.2-HEK293 cells, and that exogenous H2S is capable of enhancing Cav3.2 function when endogenous H2S production by CSE is inhibited. In addition, Na2S is considered a more potent H2S donor than NaHS in vitro as well as in vivo.
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Stigmatized as a toxic environmental pollutant for centuries, hydrogen sulfide (H2S) has gained recognition over the last decade as an important gasotransmitter that functions in physiological and pathophysiological conditions, such as atherosclerosis. ⋯ The efficiency and safety profile of H2S-based therapeutic approaches should be refined, and the mechanisms by which H2S exerts its beneficial effects should be elucidated to develop more specific and potent therapeutic strategies to treat atherosclerosis. Whether the therapeutic effects of H2S in animal studies are transferable to clinical studies merits future investigation.
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High levels of homocysteine (Hcy), known as hyperhomocysteinemia are associated with neurovascular diseases. H2S, a metabolite of Hcy, has potent anti-oxidant and anti-inflammatory activities; however, the effect of H2S has not been explored in Hcy (IC)-induced neurodegeneration and neurovascular dysfunction in mice. Therefore, the present study was designed to explore the neuroprotective role of H2S on Hcy-induced neurodegeneration and neurovascular dysfunction. ⋯ The increased expression of matrix metalloproteinase (MMP) MMP9, MMP2 and decreased expression of tissue inhibitor of metalloproteinase (TIMP) TIMP-1, TIMP-2, tight junction proteins (zonula occulden 1) in Hcy-treated group indicate neurovascular remodeling. Interestingly, NaHS treatment significantly attenuated Hcy-induced oxidative stress, memory deficit, neurodegeneration, neuroinflammation and cerebrovascular remodeling. The results indicate that H2S is effective in providing protection against neurodegeneration and neurovascular dysfunction.
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Cellular signalling · Nov 2013
Dysregulation of cystathionine γ-lyase (CSE)/hydrogen sulfide pathway contributes to ox-LDL-induced inflammation in macrophage.
Hydrogen sulfide (H2S), mainly produced by cystathionine γ-lyase (CSE) in vascular system, emerges as a novel gasotransmitter exerting anti-inflammatory and anti-atherosclerotic effects. Alterations of CSE/H2S pathway may thus be involved in atherosclerosis pathogenesis. However, the underlying mechanisms are poorly understood. ⋯ Furthermore, inhibitors of NF-κB (PDTC), ERK (U0126 and PD98059) and JNK (SP600125) partially blocked the suppression by ox-LDL on the CSE mRNA levels. Taken together, the findings demonstrate that ox-LDL may down-regulate the CSE/H2S pathway, which plays an anti-inflammatory role in ox-LDL-stimulated macrophage by suppressing JNK/NF-κB signaling. The study reveals new therapeutic strategies for atherosclerosis, based on modulating CSE/H2S pathway.
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Hydrogen sulfide (H2 S), a toxic volcanic gas, functions as a gaseous physiological and pathophysiological molecule. Recently we have shown that H2 S elicits acute pain through the activation of transient receptor potential ankyrin 1 (TRPA1), which is expressed mainly in primary nociceptive neurons. We also demonstrated enhancement of H2 S-induced TRPA1 activation and pain under inflammatory acidic conditions, but the underlying mechanism has not been elucidated. ⋯ H2 S failed to increase the intracellular ROS level and only slightly decreased pHi. These results suggest that H2 S directly activates TRPA1 and that its increment of diffusion into cells may be involved in the potentiation of TRPA1 activation under external acidic conditions. Thus, our study supports the pathophysiological functions of H2 S in inflammatory pain.