Proteome alteration of U251 human astrocytoma cell after inhibiting retinoic acid synthesis.
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, mitochondrial 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.
Zhang
Ming
M
Bio-X Center, Shanghai Jiao Tong University, Huashan Road 1954, Shanghai, 200030, China. lifeming@gmail.com
Wan
Chunling
C
Ji
Baohu
B
Zhang
Zhao
Z
Zhu
Hui
H
Tian
Nan
N
La
Yujuan
Y
Huang
Ke
K
Jiang
Lei
L
He
Guang
G
Gao
Linhan
L
Zhao
Xinzhi
X
Shi
Yongyong
Y
Huang
Gang
G
Feng
Guoyin
G
He
Lin
L
D000080462:Acyclic Monoterpenes; D000818:Animals; D001254:Astrocytoma / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D019295:Computational Biology / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008969:Molecular Sequence Data; D039821:Monoterpenes / Q000494:pharmacology; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014212:Tretinoin / Q000378:metabolism*
D000080462:Acyclic Monoterpenes; D039821:Monoterpenes; D020543:Proteome; D014212:Tretinoin; D050543:Phosphoglycerate Dehydrogenase; C007076:citral