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

Takashi Toyama, Yasuhiro Shinkai, Daigo Sumi, Yoshito Kumagai

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)86-90
Number of pages5
JournalToxicology and Applied Pharmacology
Volume249
Issue number1
DOIs
Publication statusPublished - 2010 Nov 15
Externally publishedYes

Keywords

  • Carbon monoxide
  • Heme oxygenase
  • Methylmercury
  • Nrf2

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology
  • Medicine(all)

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