Accumulation of carbonyl proteins in the brain of mouse model for methylglyoxal detoxification deficits

Shin Koike, Kazuya Toriumi, Sakura Kasahara, Yosuke Kibune, Yo Ichi Ishida, Takashi Dan, Toshio Miyata, Makoto Arai, Yuki Ogasawara

Research output: Contribution to journalArticlepeer-review

Abstract

Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, cat-egorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between car-bonyl stress and the pathogenesis of this disease is not well established. In this study, glyoxalase 1(Glo1)-knockout and vitamin B6-deficient mice (KO/VB6 (-) mice), which are susceptible to methyl-glyoxal (MGO)-induced oxidative damages, were used as a CS-SCZ model to analyze MGO-modi-fied protein and the carbonyl stress status in the brain. A comparison between Wild/VB6(+) mice and KO/VB6(−) mice for accumulated carbonyl proteins levels, with several advanced glycation end products (AGEs) in the brain, revealed that carbonyl protein levels with the Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl) ornithine (MG-H1) moiety were significantly increased in the hippocampus, pre-frontal cortex, striatum, cerebral cortex, and brainstem regions of the brain in KO/VB6(−) mice. Moreover, two-dimensional electrophoresis and Liquid chromatography-tandem mass spectrome-try analysis showed MG-H1-modified arginine residues in mitochondrial creatine kinase, beta-ad-renergic receptor kinase 1, and T-complex protein in the hippocampus region of KO/VB6(−) mice, but not in Wild/VB6(+) mice. In particular, MG-H1 modification of mitochondrial creatine kinase was quite notable. These results suggest that further studies focusing on MG-H1-modified and accumulated proteins in the hippocampus may reveal the onset mechanism of CS-SCZ induced by MGO-induced oxidative damages.

Original languageEnglish
Article number574
JournalAntioxidants
Volume10
Issue number4
DOIs
Publication statusPublished - 2021 Apr

Keywords

  • Carbonyl stress
  • Methylglyoxal-induced oxidative damages
  • Mitochondrial creatine kinase
  • Pyridoxamine
  • Scavenger
  • Schizophrenia

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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