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Proteome alteration of U251 human astrocytoma cell after inhibiting retinoic acid synthesis

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Abstract

Retinoic acid (Ra) is crucial for the patterning and neuronal differentiation in the central nervous system (CNS). Ra deficiency in animals disrupts the motor activities and memory abilities. The molecular mechanisms underlying these behavior abnormalities remain largely unknown. In the current study, we treated the astrocytoma cells with citral, an inhibitor of Ra synthesis. We analyzed the differences in the protein concentrations between the treated and untreated astrocytoma cells by two-dimensional gel electrophoresis (2-DE), Imagemaster software, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In total, 39 of 46 altered protein spots with significant mascot scores were identified representing 36 proteins, that were involved in significantly altered glutamate metabolism, lipid metabolism, mitochrondrial function, and oxidative stress response by Ingenuity Pathway Analysis (IPA). Altered 3-phosphoglycerate dehydrogenase (PHGDH) was also observed in western blot. These data provide some clues for explaining the behavioral changes caused by Ra deficiency, and support the hypothesis that Ra signaling is associated with some symptoms of neurodegenerative disorders and schizophrenia.

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Acknowledgments

The study was supported by 973 Program (2006CB910600), National Natural Science Foundation of China (30700203), Shanghai Leading Academic Discipline Project (B205), 863 Program of China, and the Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-YW-R-01). We thank all the proteomics group members for their helpful suggestions regarding both experiments and the manuscript.

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Authors and Affiliations

  1. Bio-X Center, Shanghai Jiao Tong University, Huashan Road 1954, Shanghai, 200030, China

    Ming Zhang, Chunling Wan, Baohu Ji, Zhao Zhang, Hui Zhu, Nan Tian, Yujuan La, Ke Huang, Guang He, Linhan Gao, Xinzhi Zhao, Yongyong Shi & Lin He

  2. Institutes for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai, 200031, China

    Ming Zhang, Chunling Wan, Baohu Ji, Zhao Zhang, Hui Zhu, Nan Tian, Yujuan La, Ke Huang, Guang He, Linhan Gao, Xinzhi Zhao & Yongyong Shi

  3. Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA

    Lei Jiang

  4. Shanghai Jiao Tong University Medical School, 280 South Chongqing Road, Shanghai, 200025, China

    Gang Huang

  5. Shanghai Institute of Mental Health, 600 South Wan Ping Road, Shanghai, China

    Guoyin Feng

  6. Institutes of Biomedical Sciences, Fudan University, 130 Dongan Road, Shanghai, 200032, China

    Lin He

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  1. Ming Zhang
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Correspondence to Chunling Wan or Lin He.

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Ming Zhang and Chunling Wan have contributed equally.

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Zhang, M., Wan, C., Ji, B. et al. Proteome alteration of U251 human astrocytoma cell after inhibiting retinoic acid synthesis. Mol Cell Biochem 323, 185–193 (2009). https://doi.org/10.1007/s11010-008-9978-z

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  • DOI: https://doi.org/10.1007/s11010-008-9978-z

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