Hydrogen sulphide regulates calcium homeostasis in microglial cells

Abstract

Hydrogen sulphide (H 2 S), which is produced endogenously from L-cysteine in mammalian tissues, has been suggested to function as a neuromodulator in the brain. However, the role of H 2 S in microglial cells is unclear. In this study, the effect of exogenous and endogenous H 2 S on intracellular calcium homeostasis was investigated in primary cultured microglial cells. Sodium hydrosulphide (NaHS), a H 2 S donor, caused a concentration-dependent (0.1-0.5 mM) increase in intracellular calcium concentration ([Ca 21 ] i ). This effect was significantly attenuated in the presence of a calcium-free extracellular solution, Gd 31 (100 lM), a nonselective Ca 21 channel blocker, or thapsigargin (2 lM), an inhibitor of the sarcoplasmic/endoplasmic reticulum Ca 21 -ATPase. These observations suggest that the increase in [Ca 21 ] i in response to H 2 S involves both calcium influx across the plasma membrane and calcium release from intracellular stores. The H 2 S-induced calcium elevation is partly attenuated by H-89, a selective cAMP-dependent protein kinase (PKA) inhibitor, but not by U73122, a phospholipase C (PLC) inhibitor, and chelerythrine, a selective protein kinase C (PKC) inhibitor, suggesting the involvement of cAMP/PKA, but not PLC/PKC/phosphoinositol-3,4,5-inositol (IP 3 ) pathway. Using RT-PCR, only cystathionine g-lyase (CSE), a H 2 S producing enzyme, was detected in primary cultures of microglia. Lowering endogenous H 2 S level with, D,L-propargylglycine and b-cyano-L-alanine, two CSE inhibitors, significantly decreased [Ca 21 ] i , suggesting that endogenous H 2 S may have a positive tonic influence on [Ca 21 ] i homeostasis. These findings support the possibility that H 2 S may serve as a neuromodulator to facilitate signaling between neurons and microglial cells.

Regulation of Colonic Ion Transport by Gasotransmitters

“…at microglial cells from the rat. 27) In these cells H 2 S stimulates both the release of stored Ca 2ϩ from thapsigargin-sensitive stores, as well as an influx of extracellular Ca 2ϩ . In the gastrointestinal tract H 2 S is known to relax smooth muscle from different species 28) and to induce anion secretion across the colonic epithelium.…”

The effect of hydrogen sulphide on experimental cerebral vasospasm

“…Vasospasm remains a leading cause of morbidity and mortality in relation to SAH. Current data suggest a role in cardiovascular tissue, its expression also in neural tissue has been shown previously (6,10). While aminooxyacetic acid (AOAA) is the major inhibitor of CBS, CSE is mainly blocked by propargylglycine (PPG) (16)…”

The Oxidative Stress of Hyperhomocysteinemia Results from Reduced Bioavailability of Sulfur-Containing Reductants

“…Stimulates the inhibitory effects of catalase and superoxide dismutase (SOD) in oxidative stress of mouse brain endothelial cells [95]. Regulates Ca 2+ homeostasis in microglial cells [96]. Inhibits TNF expression in microglial cultures [97].…”