Identification of proteins differentially expressed by glutamate treatment in cerebral cortex of neonatal rats

다국어 초록 (Multilingual Abstract)

Glutamate leads to neuronal cell damage by generating neurotoxicity during brain development. The objective of this study is to identify proteins that differently expressed by glutamate treatment in neonatal cerebral cortex. Sprague-Dawley rat pups (post-natal day 7) were intraperitoneally injected with vehicle or glutamate (10 mg/kg). Brain tissues were isolated 4 h after drug treatment and fixed for morphological study. Moreover, cerebral cortices were collected for protein study. Two-dimensional gel electrophoresis and mass spectrometry were carried out to identify specific proteins. We observed severe histopathological changes in glutamate-exposed cerebral cortex. We identified various proteins that differentially expressed by glutamate exposure. Identified proteins were thioredoxin, peroxiredoxin 5, ubiquitin carboxy-terminal hydrolase L1, proteasome subunit alpha proteins, isocitrate dehydrogenase, and heat shock protein 60. Heat shock protein 60 was increased in glutamate exposed condition. However, other proteins were decreased in glutamate-treated animals. These proteins are related to anti-oxidant, protein degradation, metabolism, signal transduction, and anti-apoptotic function. Thus, our findings can suggest that glutamate leads to neonatal cerebral cortex damage by regulation of specific proteins that mediated with various functions.

참고문헌 (Reference)

1 Barnes LD, "Yeast diphosphopyridine nucleotide specific isocitrate dehydrogenase. Purification and some properties" 10 (10): 3939-3944, 1971

2 Alves-Rodrigues A, "Ubiquitin, cellular inclusions and their role in neurodegeneration" 21 (21): 516-520, 1998

3 Leroy E, "The ubiquitin pathway in Parkinson’s disease" 395 (395): 451-452, 1998

4 Maher P, "The role of monoamine metabolism in oxidative glutamate toxicity" 16 (16): 6394-6401, 1996

5 Tanaka K, "The proteasome : overview of structure and functions" 85 (85): 12-36, 2009

6 Wilkinson KD, "The neuron-specific protein PGP 9.5 is a ubiquitin carboxyl-terminal hydrolase" 246 (246): 670-673, 1989

7 Yang JL, "The excitatory neurotransmitter glutamate stimulates DNA repair to increase neuronal resiliency" 132 (132): 405-411, 2011

8 김요섭, "The Role of Peroxiredoxin Family in Cancer Signaling" 대한암예방학회 24 (24): 65-71, 2019

9 Sun J, "Role of UCHL1/ubiquitin in acute testicular ischemia-reperfusion injury" 366 (366): 539-544, 2008

10 Plaisant F, "Recombinant peroxiredoxin 5 protects against excitotoxic brain lesions in newborn mice" 34 (34): 862-872, 2003

11 Bilguvar K, "Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration" 110 (110): 3489-3494, 2013

12 Sazanov LA, "Proton-translocating transhydrogenase and NADand NADP-linked isocitrate dehydrogenases operate in a substrate cycle which contributes to fine regulation of the tricarboxylic acid cycle activity in mitochondria" 344 (344): 109-116, 1994

13 Choi DW, "Pharmacology of glutamate neurotoxicity in cortical cell culture : attenuation by NMDA" 8 (8): 185-196, 1988

14 Hattori F, "Peroxiredoxins in the central nervous system" 44 : 357-374, 2007

15 Lee DG, "Peroxiredoxin 5 prevents iron overload-induced neuronal death by inhibiting mitochondrial fragmentation and endoplasmic reticulum stress in mouse hippocampal HT-22 cells" 102 : 10-19, 2018

16 Takagi Y, "Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage" 96 (96): 4131-4136, 1999

17 Rosa SG, "Monosodium glutamate induced nociception and oxidative stress dependent on time of administration, age of rats and susceptibility of spinal cord and brain regions" 351 : 64-73, 2018

18 Michaelis EK, "Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging" 54 (54): 369-415, 1998

19 Bubber P, "Mitochondrial abnormalities in Alzheimer brain : mechanistic implications" 57 (57): 695-703, 2005

20 Cabiscol E, "Mitochondrial Hsp60, resistance to oxidative stress, and the labile iron pool are closely connected in Saccharomyces cerevisiae" 277 (277): 44531-44538, 2002

21 Shen GN, "Knockdown of peroxiredoxin V increases glutamateinduced apoptosis in HT22 hippocampal neuron cells" 17 (17): 7827-7834, 2018

22 Rosenberger K, "Intrathecal heat shock protein 60 mediates neurodegeneration and demyelination in the CNS through a TLR4-and MyD88-dependent pathway" 10 : 5-, 2015

23 Lewis SB, "Identification and preliminary characterization of ubiquitin C terminal hydrolase 1(UCHL1)as a biomarker of neuronal loss in aneurysmal subarachnoid hemorrhage" 88 (88): 1475-1484, 2010

24 Tapiero H, "Glutamine and glutamate" 56 (56): 446-457, 2002

25 Rössler OG, "Glutamate-induced cell death of immortalized murine hippocampal neurons : neuroprotective activity of heme oxygenase-1, heat shock protein 70, and sodium selenite" 362 (362): 253-257, 2004

26 Castaneda-Cabral JL, "Glutamate neonatal excitotoxicity modifies VEGF-A, VEGF-B, VEGFR-1and VEGFR-2 protein expression profiles during postnatal development of the cerebral cortex and hippocampus of male rats" 63 (63): 17-27, 2017

27 Gudino-Cabrera G, "Excitotoxicity triggered by neonatal monosodium glutamate treatment and blood-brain barrier function" 45 (45): 653-659, 2014

28 Johnston MV, "Excitotoxicity in perinatal brain injury" 15 (15): 234-240, 2005

29 Safonova OA, "Effects of 2, 4-dimethoxyphenyl biguanide on glutathione system activity in rat tissues in brain ischemia-reperfusion" 151 (151): 556-559, 2011

30 Keller JN, "Decreased levels of proteasome activity and proteasome expression in aging spinal cord" 98 (98): 149-156, 2000

31 Moiseeva TN, "DNA damage-induced ubiquitylation of proteasome controls its proteolytic activity" 4 (4): 1338-1348, 2013

32 Minich T, "Cytosolic and mitochondrial isoforms of NADP+-dependent isocitrate dehydrogenases are expressed in cultured rat neurons, astrocytes, oligodendrocytes and microglial cells" 86 (86): 605-614, 2003

33 Johnson RB, "Cloning and characterization of the yeast chaperonin HSP60 gene" 84 (84): 295-302, 1989

34 Foran L, "Auditory hindbrain atrophy and anomalous calcium binding protein expression after neonatal exposure to monosodium glutamate" 344 : 406-417, 2017

35 Grelli KN, "Alteration of isocitrate dehydrogenase following acute ischemic injury as a means to improve cellular energetic status in neuroadaptation" 12 (12): 849-860, 2013

36 De Felice FG, "Abeta oligomers induce neuronal oxidative stress through an Nmethyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine" 282 (282): 11590-11601, 2017