Potential neuroprotective effect of γ-glutamylcysteine ethyl ester on rat brain against kainic acid-induced excitotoxicity

被引：14

作者：

Yalcin, Ayfer ^{[1
]}

Armagan, Guliz ^{[1
]}

Turunc, Ezgi ^{[1
]}

Konyalioglu, Sibel ^{[1
]}

Kanit, Lutfiye ^{[2
]}

机构：

[1] Ege Univ, Fac Pharm, Dept Biochem, TR-35100 Izmir, Turkey

[2] Ege Univ, Fac Med, Dept Physiol, TR-35100 Izmir, Turkey

来源：

FREE RADICAL RESEARCH | 2010年 / 44卷 / 05期

关键词：

INDUCED OXIDATIVE STRESS; TUMOR-SUPPRESSOR P53; INDUCED CELL-DEATH; DNA FRAGMENTATION; UP-REGULATION; STATUS EPILEPTICUS; CEREBRAL-ISCHEMIA; INDUCED SEIZURES; GLUTATHIONE ELEVATION; KAINATE INJECTION;

D O I：

10.3109/10715761003645964

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The aim of this study was to investigate the effect of gamma-Glutamylcysteine Ethyl Ester (GCEE) on the levels of GSH, caspase-3 activity, DNA damage and the expressions of Bcl-2, Bax and p53 mRNAs in rat hippocampus after status epilepticus (SE) induced by systemic kainic acid (KA). The male rats were divided into four groups as controls, KA (10 mg/kg), GCEE (10 mg/kg) and KA+GCEE. Glutathione (GSH) levels and caspase-3 activity were determined spectrophotometrically and colourimetrically, respectively. DNA damage and Bcl-2, Bax and p53 mRNA expressions were quantified by comet assay and reverse transcription followed by RT-PCR, respectively. KA treatment significantly depleted GSH levels, induced DNA damage, caspase-3 activity and the expressions of p53 and Bax mRNA. GCEE treatment protected GSH levels, decreased DNA damage and the levels of p53 and Bax/Bcl-2 mRNA against KA injection. These results indicate that GCEE treatment at the dose of 10 mg/kg is capable to protect the depleted levels of GSH and shows an anti-apoptotic activity due to the decreased levels of apoptotic biomarkers in the rat hippocampus after SE induced by KA.

引用

页码：513 / 521

页数：9

共 66 条

[1] Expression, interaction, and proteolysis of death-associated protein kinase and p53 within vulnerable and resistant hippocampal subfields following seizures [J].

Araki, T ;

Shinoda, S ;

Schindler, CK ;

Quan-Lan, J ;

Meller, R ;

Taki, W ;

Simon, RP ;

Henshall, DC .

HIPPOCAMPUS, 2004, 14 (03) :326-336

[2] Interleukin-10 prevents glutamate-mediated cerebellar granule cell death by blocking caspase-3-like activity [J].

Bachis, A ;

Colangelo, AM ;

Vicini, S ;

Doe, PP ;

De Bernardi, MA ;

Brooker, G ;

Mocchetti, I .

JOURNAL OF NEUROSCIENCE, 2001, 21 (09) :3104-3112

[3] Multiple roles of the tumor suppressor p53 [J].

Bargonetti, J ;

Manfredi, JJ .

CURRENT OPINION IN ONCOLOGY, 2002, 14 (01) :86-91

[4] MECHANISMS OF EXCITOTOXICITY IN NEUROLOGIC DISEASES [J].

BEAL, MF .

FASEB JOURNAL, 1992, 6 (15) :3338-3344

[5] Differential regulation of apoptosis-related genes in resistant and vulnerable subfields of the rat epileptic hippocampus [J].

Becker, AJ ;

Gillardon, F ;

Blümcke, I ;

Langendörfer, D ;

Beck, H ;

Wiestler, OD .

MOLECULAR BRAIN RESEARCH, 1999, 67 (01) :172-176

[6] γ-glutamylcysteine ethyl ester protection of proteins from Aβ(1-42)-mediated oxidative stress in neuronal cell culture:: A proteomics approach [J].

Boyd-Kimball, D ;

Sultana, R ;

Poon, HF ;

Mohmmad-Abdul, H ;

Lynn, BC ;

Klein, JB ;

Butterfield, DA .

JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 79 (05) :707-713

[7] γ-glutamylcysteine ethyl ester-induced up-regulation of glutathione protects neurons against Aβ(1-42)-mediated oxidative stress and neurotoxicity:: Implications for Alzheimer's disease [J].

Boyd-Kimball, D ;

Sultana, R ;

Abdul, HM ;

Butterfield, DA .

JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 79 (05) :700-706

[8] Nimesulide limits kainate-induced oxidative damage in the rat hippocampus [J].

Candelario-Jalil, E ;

Ajamieh, HH ;

Sam, S ;

Martínez, G ;

Fernández, OSL .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2000, 390 (03) :295-298

[9] Selective vulnerability to kainate-induced oxidative damage in different rat brain regions [J].

Candelario-Jalil, E ;

Al-Dalain, SM ;

Castillo, R ;

Martínez, G ;

Fernández, OSL .

JOURNAL OF APPLIED TOXICOLOGY, 2001, 21 (05) :403-407

[10] In vitro and in vivo neuroprotection by γ-glutamylcysteine ethyl ester against MPTP:: Relevance to the role of glutathione in Parkinson's disease [J].

Chinta, Shankar J. ;

Rajagopalan, Subramanian ;

Butterfield, D. Allan ;

Andersen, Julie K. .

NEUROSCIENCE LETTERS, 2006, 402 (1-2) :137-141

← 1 2 3 4 5 6 7 →