Hydrogen sulphide regulates calcium homeostasis in microglial cells

✍ Scribed by Shiau Wei Lee; Ye-Shi Hu; Li-Fang Hu; Qing Lu; Gavin S. Dawe; Philip K. Moore; Peter T.-H. Wong; Jin-Song Bian

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 450 KB
• Volume: 54
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.20362

✦ Synopsis

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.

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