Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance.

Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance. Research Abstract Details 

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Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance. Abstract Text:

R Hamaoka,J Fujii,J Miyagawa,M Takahashi,M Kishimoto,M Moriwaki,K Yamamoto,Y Kajimoto,Y Yamasaki,T Hanafusa,Y Matsuzawa,N Taniguchi,

To determine the role of the polyol metabolizing pathway under hyperglycemic conditions, the effects of aldose reductase (AR) on the cellular functions of pancreatic beta-cells were examined. Stable transfectants of rat AR cDNA were obtained with a pancreatic beta-cell line, HIT, in which a negligible amount of AR was originally expressed. Overproduction of AR triggered DNA fragmentation, as judged with the TUNEL method and agarose gel electrophoresis. Morphological analysis by electron microscopy also clearly showed apoptosis of the AR-overexpressing HIT cells. Induction by interleukin-1beta of gene expression such as those of an inducible form of nitric oxide synthase (NOS-II) and Mn-superoxide dismutase (Mn-SOD), was much lower in the transfectants than in the control cells, while the expression of constitutively expressed genes such as those for Cu,Zn-superoxide dismutase and insulin was not changed. The susceptibility to interleukin-1beta stimulation of the expression of the NOS II and Mn-SOD genes was due to suppressed NF-kappaB activity, which is essential for the expression of these genes. In addition, the intracellular NADPH/NADP+ ratio was considerably lower in the AR-transfected cells than in control cells. Thus, the overexpression of AR in pancreatic beta-cells induced apoptosis that may be caused by a redox imbalance.

Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance. Publishing Authors By Initials

R Hamaoka,J Fujii,J Miyagawa,M Takahashi,M Kishimoto,M Moriwaki,K Yamamoto,Y Kajimoto,Y Yamasaki,T Hanafusa,Y Matsuzawa,N Taniguchi,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of biochemistry

VOLUME: 126

Page Numbers: 41-7

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Jul

YEAR: 1999

Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance. Information

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LANGUAGE: eng

NlmUniqueID: 376600

Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: metabolism

Chemical & Substance for Abstract: Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance. Information

Substance Name: Superoxide Dismutase

Registry Number: EC 1.15.1.1

Grant and Affiliation Information for Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance.

AFFILIATION: Department of Biochemistry, Graduate School of Medicine, Osaka University Medical School, Suita 565-0871, Japan.

Country: JAPAN

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MEDLINETA: J Biochem

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