Carbon monoxide derived from heme oxygenase-2 mediates reduction of methylmercury toxicity in SH-SY5Y cells

Takashi Toyama, Yasuhiro Shinkai, Daigo Sumi, Yoshito Kumagai

研究成果: Article査読

5 被引用数 (Scopus)

抄録

We examined the contribution of carbon monoxide (CO), an enzymatic product of heme oxygenase (HO), to methylmercury (MeHg) cytotoxicity in SH-SY5Y cells, because this gas molecule is reported to activate Nrf2, which plays a protective role against MeHg-mediated cell damage. Exposure of SH-SY5Y cells to CO gas resulted in protection against MeHg cytotoxicity, with activation of Nrf2. Interestingly, pretreatment with tin-protoporphyrin IX, a specific inhibitor of HO, caused a reduction in basal Nrf2 activity and thus enhanced sensitivity to MeHg. No induction of isoform 1 of HO (HO-1) was seen during MeHg exposure, but constitutive expression of isoform 2 (HO-2) occurred, suggesting that CO produced by HO-2 is the main participant in the protection against MeHg toxicity. Studies of small interfering RNA-mediated knockdown of HO-2 in the cells supported this possibility. Our results suggest that CO gas and its producing enzyme HO-2 are key molecules in cellular protection against MeHg, presumably through basal activation of Nrf2.

本文言語English
ページ(範囲)86-90
ページ数5
ジャーナルToxicology and Applied Pharmacology
249
1
DOI
出版ステータスPublished - 2010 11 15
外部発表はい

ASJC Scopus subject areas

  • 毒物学
  • 薬理学

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