Mikami Yoshinori, Kimura Hideo
Department of Molecular Pharmacology; National Institute of Neuroscience; National Center of Neurology and Psychiatry; Kodaira, Japan.
Commun Integr Biol. 2012 Mar 1;5(2):169-71. doi: 10.4161/cib.18679.
Since our initial demonstrations that hydrogen sulfide (H(2)S) may function as a neuromodulator in the brain and a smooth muscle relaxant in the vascular system, accumulating evidence shows that H(2)S may function as a signaling molecule. We and others also found that H(2)S has a cytoprotective effect. Because H(2)S is well-known toxic gas, a cytoprotective role has been overlooked. H(2)S protects neurons from oxidative stress. It also protects cardiac muscle from ischemia-reperfusion injury. The finding led to the application of H(2)S to the bypass surgery patients in Phase II clinical trial. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are well known as H(2)S-producing enzymes. We recently demonstrated that the other H(2)S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3MST) along with cysteine aminotransferase (CAT) is localized to neurons in the brain and to the vascular endothelium. However, the regulation of H(2)S production by 3MST/CAT pathway had not been well understood. The present study shows that H(2)S production by 3MST/CAT pathway is regulated by Ca(2+) and that H(2)S protects retinal photoreceptor cells from light induced degeneration by suppressing excessive Ca(2+) influx caused by intense light.
自从我们最初证明硫化氢（H₂S）可能在大脑中作为神经调节剂发挥作用，并在血管系统中作为平滑肌松弛剂以来，越来越多的证据表明H₂S可能作为一种信号分子发挥作用。我们和其他人还发现H₂S具有细胞保护作用。由于H₂S是一种众所周知的有毒气体，其细胞保护作用一直被忽视。H₂S可保护神经元免受氧化应激。它还能保护心肌免受缺血再灌注损伤。这一发现促使H₂S在二期临床试验中应用于搭桥手术患者。胱硫醚β合酶（CBS）和胱硫醚γ裂解酶（CSE）是众所周知的产生H₂S的酶。我们最近证明，另一种产生H₂S的酶，3-巯基丙酮酸硫转移酶（3MST）与半胱氨酸转氨酶（CAT）定位于大脑中的神经元和血管内皮。然而，3MST/CAT途径对H₂S产生的调节尚未得到很好的理解。本研究表明，3MST/CAT途径产生H₂S受Ca²⁺调节，并且H₂S通过抑制强光引起的过量Ca²⁺内流，保护视网膜光感受器细胞免受光诱导的退化。
