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.
- Carbonyl stress
- Methylglyoxal-induced oxidative damages
- Mitochondrial creatine kinase
ASJC Scopus subject areas
- Molecular Biology
- Clinical Biochemistry
- Cell Biology