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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)153-162
Number of pages10
JournalToxicology and Applied Pharmacology
Volume235
Issue number2
DOIs
Publication statusPublished - Mar 1 2009
Externally publishedYes

Fingerprint

Cell death
Cadmium
Cell Death
Necrosis
U937 Cells
Mitochondrial Membrane Potential
Cricetulus
Ovary
Membranes
Death Domain Receptors
Mitochondria
Acids
Calpain
necrostatin-1
Reactive Oxygen Species
Peptide Hydrolases
Calcium

Keywords

  • Cadmium
  • Mitochondria
  • Necrosis
  • Necrostatin-1
  • NF-κB
  • RIP1

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Attenuation of cadmium-induced necrotic cell death by necrostatin-1 : Potential necrostatin-1 acting sites. / Hsu, Tzu Sheng; Yang, Pei Ming; Tsai, Jia Shiuan; Lin, Lih Yuan.

In: Toxicology and Applied Pharmacology, Vol. 235, No. 2, 01.03.2009, p. 153-162.

Research output: Contribution to journalArticle

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