Carbon monoxide stimulates global protein methylation via its inhibitory action on cystathionine β-synthase

Takehiro Yamamoto, Naoharu Takano, Kyoko Ishiwata, Makoto Suematsu

研究成果: Article査読

28 被引用数 (Scopus)

抄録

Although carbon monoxide derived from heme oxygenase has been reported to exert diverse biological actions in mammals, macromolecules responsible for its direct reception and functional outcomes of the gas binding remain largely unknown. Based on our previous results in vivo suggesting carbon monoxide serves as an inhibitor of cystathionine β-synthase that rate-limits trans-sulfuration pathway for generation of hydrogen sulfide, we have herein hypothesized that the gas might serve as a regulator of protein methylation through accelerating turnover of remethylation cycle residing at the upstream of the enzyme. Metabolomic analysis in human monoblastic leukemia U937 cells in culture revealed that application of carbon monoxide-releasing molecules caused increases in methionine and S-adenosylmethionine and a decrease in cystathionine in the cells, suggesting the cystathionine β-synthase inhibition by carbon monoxide. Under these circumstances, the cells exhibited global protein arginine methylation: this event was also reproduced by the cell treatment with hemin, a heme oxygenase-1 inducer. The protein arginine methylation elicited by carbon monoxide was attenuated by knocking down cystathionine β-synthase with its small interfering RNA or by blocking S-adenosylhomocysteine hydrolase with adenosine dialdehyde, suggesting remethylation cycling is necessary to trigger the methylation processing. Furthermore, proteins under-going the carbon monoxide-induced arginine methylation involved histone H3 proteins, suggesting chromatin modification by the gas. Collectively with our studies in vivo showing its inhibitory action on endogenous hydrogen sulfide production, the current results suggest that not only inhibition of transsulfuration pathway for H2S generation but also activation of protein methylation accounts for notable biological actions of carbon monoxide via the cystathionine β-synthase inhibition.

本文言語English
ページ(範囲)96-100
ページ数5
ジャーナルJournal of Clinical Biochemistry and Nutrition
48
1
DOI
出版ステータスPublished - 2011 1

ASJC Scopus subject areas

  • 医学(その他)
  • 栄養および糖尿病
  • 臨床生化学

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