Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits
Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl stress and the pathogenesis of this disease is not well established. In this study, glyoxalase 1(Glo1)-knock...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-04-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/10/4/574 |
| _version_ | 1797538386542592000 |
|---|---|
| author | Shin Koike Kazuya Toriumi Sakura Kasahara Yosuke Kibune Yo-ichi Ishida Takashi Dan Toshio Miyata Makoto Arai Yuki Ogasawara |
| author_facet | Shin Koike Kazuya Toriumi Sakura Kasahara Yosuke Kibune Yo-ichi Ishida Takashi Dan Toshio Miyata Makoto Arai Yuki Ogasawara |
| author_sort | Shin Koike |
| collection | DOAJ |
| description | Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl 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 methylglyoxal (MGO)-induced oxidative damages, were used as a CS-SCZ model to analyze MGO-modified 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, prefrontal cortex, striatum, cerebral cortex, and brainstem regions of the brain in KO/VB6(−) mice. Moreover, two-dimensional electrophoresis and Liquid chromatography-tandem mass spectrometry analysis showed MG-H1-modified arginine residues in mitochondrial creatine kinase, beta-adrenergic 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. |
| first_indexed | 2024-03-10T12:29:49Z |
| format | Article |
| id | doaj.art-494c195c7e394199ba65277b880013f9 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T12:29:49Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-494c195c7e394199ba65277b880013f92023-11-21T14:42:16ZengMDPI AGAntioxidants2076-39212021-04-0110457410.3390/antiox10040574Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification DeficitsShin Koike0Kazuya Toriumi1Sakura Kasahara2Yosuke Kibune3Yo-ichi Ishida4Takashi Dan5Toshio Miyata6Makoto Arai7Yuki Ogasawara8Department of Analytical Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, JapanSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, JapanDepartment of Analytical Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, JapanDepartment of Analytical Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, JapanDepartment of Molecular and Cellular Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, JapanDivision of Molecular Medicine and Therapy, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanDivision of Molecular Medicine and Therapy, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanSchizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, JapanDepartment of Analytical Biochemistry, Meiji Pharmaceutical University, Tokyo 204-8588, JapanRecent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl 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 methylglyoxal (MGO)-induced oxidative damages, were used as a CS-SCZ model to analyze MGO-modified 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, prefrontal cortex, striatum, cerebral cortex, and brainstem regions of the brain in KO/VB6(−) mice. Moreover, two-dimensional electrophoresis and Liquid chromatography-tandem mass spectrometry analysis showed MG-H1-modified arginine residues in mitochondrial creatine kinase, beta-adrenergic 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.https://www.mdpi.com/2076-3921/10/4/574carbonyl stresspyridoxaminescavengerschizophreniamethylglyoxal-induced oxidative damagesmitochondrial creatine kinase |
| spellingShingle | Shin Koike Kazuya Toriumi Sakura Kasahara Yosuke Kibune Yo-ichi Ishida Takashi Dan Toshio Miyata Makoto Arai Yuki Ogasawara Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits Antioxidants carbonyl stress pyridoxamine scavenger schizophrenia methylglyoxal-induced oxidative damages mitochondrial creatine kinase |
| title | Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits |
| title_full | Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits |
| title_fullStr | Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits |
| title_full_unstemmed | Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits |
| title_short | Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits |
| title_sort | accumulation of carbonyl proteins in the brain of mouse model for methylglyoxal detoxification deficits |
| topic | carbonyl stress pyridoxamine scavenger schizophrenia methylglyoxal-induced oxidative damages mitochondrial creatine kinase |
| url | https://www.mdpi.com/2076-3921/10/4/574 |
| work_keys_str_mv | AT shinkoike accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits AT kazuyatoriumi accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits AT sakurakasahara accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits AT yosukekibune accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits AT yoichiishida accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits AT takashidan accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits AT toshiomiyata accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits AT makotoarai accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits AT yukiogasawara accumulationofcarbonylproteinsinthebrainofmousemodelformethylglyoxaldetoxificationdeficits |