Laboratory of Pharmacology, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Laboratory of Pharmacology, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, 060-0818, Japan.
Eur J Pharmacol. 2021 Jan 15;891:173684. doi: 10.1016/j.ejphar.2020.173684. Epub 2020 Oct 29.
Hydrogen sulfide (HS) has a variety of physiological functions. HS reportedly increases intracellular Ca concentration ([Ca]) in astrocytes. However, the precise mechanism and functional role of this increase are not known. Here, we examined the effects of HS on [Ca] in astrocytes from the rat spinal cord and whether HS affects ATP-induced Ca signaling, which is known to be involved in synaptic function. NaS (150 μM), an HS donor, produced a nontoxic increase in [Ca]. The [Ca] increase by NaS was inhibited by Ca depletion in the endoplasmic reticulum (ER) but not by removal of extracellular Ca, indicating that HS releases Ca from the ER. On the other hand, NaS inhibited ATP-induced [Ca] increase when NaS clearly increased [Ca] in the astrocytes, which was not suppressed by a reducing agent. In addition, NaS had no effect on intracellular cyclic AMP (cAMP) level. These results indicate that oxidative post-translational modification of proteins and cAMP are not involved in the inhibitory effect of HS on ATP-induced Ca signaling. We conclude that HS indirectly inhibits ATP-induced Ca signaling by decreasing Ca content in the ER in astrocytes. In this way, HS may influence intercellular communication between astrocytes and neurons, thereby contributing to neuronal signaling in the nervous system.
硫化氢 (HS) 具有多种生理功能。据报道，HS 可增加星形胶质细胞内的 Ca 浓度 ([Ca])。然而，这种增加的确切机制和功能作用尚不清楚。在这里，我们研究了 HS 对大鼠脊髓星形胶质细胞中 [Ca] 的影响，以及 HS 是否影响已知参与突触功能的 ATP 诱导的 Ca 信号转导。HS 供体 NaS（150 μM）产生非毒性的 [Ca] 增加。NaS 引起的 [Ca] 增加被内质网 (ER) 中的 Ca 耗竭抑制，但不受细胞外 Ca 去除的影响，表明 HS 从 ER 中释放 Ca。另一方面，当 NaS 明显增加星形胶质细胞中的 [Ca] 时，NaS 抑制了 ATP 诱导的 [Ca] 增加，还原剂对此没有抑制作用。此外，NaS 对细胞内环磷酸腺苷 (cAMP) 水平没有影响。这些结果表明，蛋白质的氧化后翻译修饰和 cAMP 均不参与 HS 对 ATP 诱导的 Ca 信号转导的抑制作用。我们得出结论，HS 通过减少星形胶质细胞内质网中的 Ca 含量间接抑制 ATP 诱导的 Ca 信号转导。通过这种方式，HS 可能会影响星形胶质细胞和神经元之间的细胞间通讯，从而促进神经系统中的神经元信号传递。
