Enhanced vulnerability to oxidative stress and induction of inflammatory gene expression in 3-phosphoglycerate dehydrogenase-deficient fibroblasts

Momoko Hamano, Yurina Haraguchi, Tomoko Sayano, Chong Zyao, Yashiho Arimoto, Yui Kawano, Kazuki Moriyasu, Miyako Udono, Yoshinori Katakura, Takuya Ogawa, Hisanori Kato, Shigeki Furuya

Research output: Contribution to journalArticle

Abstract

l-Serine (l-Ser) is a necessary precursor for the synthesis of proteins, lipids, glycine, cysteine, d-serine, and tetrahydrofolate metabolites. Low l-Ser availability activates stress responses and cell death; however, the underlying molecular mechanisms remain unclear. l-Ser is synthesized de novo from 3-phosphoglycerate with 3-phosphoglycerate dehydrogenase (Phgdh) catalyzing the first reaction step. Here, we show that l-Ser depletion raises intracellular H 2 O 2 levels and enhances vulnerability to oxidative stress in Phgdh-deficient mouse embryonic fibroblasts. These changes were associated with reduced total glutathione levels. Moreover, levels of the inflammatory markers thioredoxin-interacting protein and prostaglandin-endoperoxide synthase 2 were upregulated under l-Ser-depleted conditions; this was suppressed by the addition of N-acetyl-l-cysteine. Thus, intracellular l-Ser deficiency triggers an inflammatory response via increased oxidative stress, and de novo l-Ser synthesis suppresses oxidative stress damage and inflammation when the external l-Ser supply is restricted.

Original languageEnglish
Pages (from-to)914-922
Number of pages9
JournalFEBS Open Bio
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

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Phosphoglycerate Dehydrogenase
Oxidative stress
Fibroblasts
Gene expression
Oxidative Stress
Gene Expression
Serine
Cysteine
Acetylcysteine
Thioredoxins
Protein Precursors
Cell death
Prostaglandin-Endoperoxide Synthases
Metabolites
Glycine
Glutathione
Proteins
Cell Death
Availability
Inflammation

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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Enhanced vulnerability to oxidative stress and induction of inflammatory gene expression in 3-phosphoglycerate dehydrogenase-deficient fibroblasts. / Hamano, Momoko; Haraguchi, Yurina; Sayano, Tomoko; Zyao, Chong; Arimoto, Yashiho; Kawano, Yui; Moriyasu, Kazuki; Udono, Miyako; Katakura, Yoshinori; Ogawa, Takuya; Kato, Hisanori; Furuya, Shigeki.

In: FEBS Open Bio, Vol. 8, No. 6, 01.06.2018, p. 914-922.

Research output: Contribution to journalArticle

Hamano, Momoko ; Haraguchi, Yurina ; Sayano, Tomoko ; Zyao, Chong ; Arimoto, Yashiho ; Kawano, Yui ; Moriyasu, Kazuki ; Udono, Miyako ; Katakura, Yoshinori ; Ogawa, Takuya ; Kato, Hisanori ; Furuya, Shigeki. / Enhanced vulnerability to oxidative stress and induction of inflammatory gene expression in 3-phosphoglycerate dehydrogenase-deficient fibroblasts. In: FEBS Open Bio. 2018 ; Vol. 8, No. 6. pp. 914-922.
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AU - Moriyasu, Kazuki

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AU - Kato, Hisanori

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