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短期给予(-)-司来吉兰和异吲哚酮对小鼠大脑皮层某些基因表达的影响。

The effect of short-term administration of (-)-deprenyl and isatin on the expressions of some genes in the mouse brain cortex.

作者信息

Fedchenko Valerii, Globa Alexander, Kaloshin Alexei, Kapitsa Inga, Nerobkova Lubov, Val'dman Elena, Buneeva Olga, Glover Vivette, Medvedev Alexei

机构信息

Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical SciencesMoscow, Russia.

出版信息

Med Sci Monit. 2008 Dec;14(12):BR269-73.

Abstract

BACKGROUND

Isatin (indoledione 2,3) is an endogenous indole found in the mammalian brain, peripheral tissues, and body fluids. It exhibits many neurophysiological and neuropharmacological effects. It shares some common molecular targets with (-)-deprenyl, a neuroprotective pharmacological drug. Some isatin effects imply a possible influence of gene expression; however, no isatin-responsive genes have yet been identified.

MATERIAL/METHODS: In this study the effects of a three-week administration of isatin (20 mg/kg) or (-)-deprenyl (1 mg/kg) on the expressions of several putative isatin/deprenyl-responsive genes in the mouse cortex were compared using real-time PCR.

RESULTS

Both treatments caused similarly significant decreases in superoxide dismutase (SOD) mRNA. Treatment of mice with either drug decreased glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, although only in the deprenyl-treated mice was this significant (p<0.01). No significant changes were found in cortex mRNA content of monoamine oxidase A or monoamine oxidase B.

CONCLUSIONS

The results suggest that isatin and (-)-deprenyl have some common target genes and this supports the idea that isatin may be an endogenous partial functional agonist of (-)-deprenyl. Since GAPDH mRNA expression is sensitive to the pharmacological treatments, these results also question the applicability of GAPDH as a reference gene in gene expression studies.

摘要

背景

异吲哚酮(吲哚二酮2,3)是一种存在于哺乳动物大脑、外周组织和体液中的内源性吲哚。它具有多种神经生理和神经药理作用。它与神经保护药物(-)-司来吉兰有一些共同的分子靶点。异吲哚酮的一些作用暗示了对基因表达可能有影响;然而,尚未鉴定出任何异吲哚酮反应基因。

材料/方法:在本研究中,使用实时PCR比较了连续三周给予异吲哚酮(20mg/kg)或(-)-司来吉兰(1mg/kg)对小鼠皮质中几种假定的异吲哚酮/司来吉兰反应基因表达的影响。

结果

两种处理均导致超氧化物歧化酶(SOD)mRNA同样显著降低。用任何一种药物处理小鼠均降低了甘油醛-3-磷酸脱氢酶(GAPDH)mRNA,尽管只有司来吉兰处理组的降低具有统计学意义(p<0.01)。单胺氧化酶A或单胺氧化酶B的皮质mRNA含量未发现显著变化。

结论

结果表明异吲哚酮和(-)-司来吉兰有一些共同的靶基因,这支持了异吲哚酮可能是(-)-司来吉兰的内源性部分功能激动剂的观点。由于GAPDH mRNA表达对药物处理敏感,这些结果也对GAPDH作为基因表达研究中的参照基因的适用性提出了质疑。

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