Attenuation of cadmium-induced necrotic cell death by necrostatin-1: Potential necrostatin-1 acting sites

Tzu Sheng Hsu, Pei Ming Yang, Jia Shiuan Tsai, Lih Yuan Lin

研究成果: 雜誌貢獻文章同行評審

24 引文 斯高帕斯(Scopus)

摘要

Cadmium (Cd) induces necrotic death in Chinese hamster ovary (CHO) K1 cells and we have established the responsible signaling pathway. Reportedly, necrostatin-1 (Nec-1) rescues cells from necrotic death by mediating through the death domain receptor (DR) signaling pathway. We show here that Nec-1 also effectively attenuates necrotic death triggered by Cd. Two other treatments that cause necrotic cell death, one can (z-VAD-fmk/TNF-α on U937 cells) and the other cannot (etherynic acid (EA) on DLD-1 cells) be rescued by Nec-1, were also studied in parallel for comparison. Results show that Nec-1 is ineffectual in modulating intracellular calcium contents, calpain activity (a downstream protease), or reactive oxygen species production. It can counteract the reduction in mitochondrial membrane potential (MMP) caused by treating CHO K1 or U937 cells with necrosis-inducing agent. However, this effect was not found in EA-treated DLD-1 cells. Notably, Nec-1 elevates NF-κB activity in the presence or absence of necrosis-inducing agents. Our study shows that, in addition to DR-mediated necrosis, Nec-1 is effective in attenuating Cd-induced necrosis. It rescues cells with reduced MMP implying that mitochondrion is its major acting site.
原文英語
頁(從 - 到)153-162
頁數10
期刊Toxicology and Applied Pharmacology
235
發行號2
DOIs
出版狀態已發佈 - 3月 1 2009
對外發佈

ASJC Scopus subject areas

  • 毒理學
  • 藥理

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