Singh K K
Johns Hopkins Oncology Center, Baltimore, MD 21231-1000, USA.
Free Radic Biol Med. 2000 Nov 15;29(10):1043-50. doi: 10.1016/s0891-5849(00)00432-9.
Aerobic organisms experience oxidative stress due to generation of reactive oxygen species during normal aerobic metabolism. In addition, environmental gamma and UV radiation, as well as several chemicals also generate reactive oxygen species, which induce oxidative stress. Thus oxidative stress constitutes a major threat to organisms living in aerobic environments. Oxidative stress induces the expression of several genes in yeast Saccharomyces cerevisiae. However, the primary sensor(s) that trigger the response is unknown. This study demonstrates that primary sensors of osmotic stress, the Sln1p-Ssk1p two-component proteins, are involved in sensing oxidative stress specifically induced by hydrogen peroxide and diamide, but not by other oxidants used in the study. Wild type and sln1-ssk1 mutant were treated with hydrogen peroxide, diamide, menadione, UV, and gamma-radiation. Results show that sln1-ssk1 mutant is only sensitive to hydrogen peroxide and diamide but not to other oxidants. S. cerevisiae contains an additional cell surface osmosensor, Sho1p, that targets the osmotic signal to Hog1p. Data is presented that shows Sho1 and Hog1 proteins are also involved in signaling oxidant-specific cellular damage. Furthermore, it is demonstrated that expression of the mammalian homolog of Hog1p provides protection from oxidative stress induced by hydrogen peroxide. These results suggest that Sln1p-Ssk1p and Sho1p signal transduction pathways participate in oxidative stress response. However, this response to oxidative stress is limited to specific oxidants.
需氧生物在正常需氧代谢过程中会因活性氧的产生而经历氧化应激。此外，环境中的伽马射线和紫外线辐射，以及几种化学物质也会产生活性氧，从而引发氧化应激。因此，氧化应激对生活在需氧环境中的生物构成了重大威胁。氧化应激会诱导酿酒酵母中多个基因的表达。然而，触发该反应的主要传感器尚不清楚。本研究表明，渗透应激的主要传感器，即Sln1p-Ssk1p双组分蛋白，参与特异性感知由过氧化氢和二酰胺诱导的氧化应激，但不参与感知本研究中使用的其他氧化剂诱导的氧化应激。用过氧化氢、二酰胺、甲萘醌、紫外线和伽马射线处理野生型和sln1-ssk1突变体。结果表明，sln1-ssk1突变体仅对过氧化氢和二酰胺敏感，而对其他氧化剂不敏感。酿酒酵母还含有另一种细胞表面渗透传感器Sho1p，它将渗透信号传递给Hog1p。现有数据表明，Sho1和Hog1蛋白也参与了氧化特异性细胞损伤的信号传导。此外，研究表明，Hog1p的哺乳动物同源物的表达可提供对过氧化氢诱导的氧化应激的保护。这些结果表明，Sln1p-Ssk1p和Sho1p信号转导途径参与氧化应激反应。然而，这种对氧化应激的反应仅限于特定的氧化剂。
