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Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II.

Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II. Research Abstract Details 

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  • Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II. Abstract Text:

    lin sunLin Sun,shetha shukairShetha Shukair,tejaswitha jairaj naikTejaswitha Jairaj Naik,farzad moazedFarzad Moazed,hossein ardehaliHossein Ardehali,lin sunLin Sun,shetha shukairShetha Shukair,tejaswitha jairaj naikTejaswitha Jairaj Naik,farzad moazedFarzad Moazed,hossein ardehaliHossein Ardehali,

    Alterations in glucose metabolism have been demonstrated for diverse disorders ranging from heart disease to cancer. The first step in glucose metabolism is carried out by the hexokinase (HK) family of enzymes. HKI and II can bind to mitochondria through their N-terminal hydrophobic regions, and their overexpression in tissue culture protects against cell death. In order to determine the relative contributions of mitochondrial binding and glucose-phosphorylating activities of HKs to their overall protective effects, we expressed full-length HKI and HKII, their truncated proteins lacking the mitochondrial binding domains, and catalytically inactive proteins in tissue culture. The overexpression of full-length proteins resulted in protection against cell death, decreased levels of reactive oxygen species, and possibly inhibited mitochondrial permeability transition in response to H(2)O(2). However, the truncated and mutant proteins exerted only partial effects. Similar results were obtained with primary neonatal rat cardiomyocytes. The HK proteins also resulted in an increase in the phosphorylation of voltage-dependent anion channel (VDAC) through a protein kinase Cepsilon (PKCepsilon)-dependent pathway. These results suggest that both glucose phosphorylation and mitochondrial binding contribute to the protective effects of HKI and HKII, possibly through VDAC phosphorylation by PKCepsilon.

    Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II. Publishing Authors By Initials

    l sunL Sun,s shukairS Shukair,tj naikTJ Naik,f moazedF Moazed,h ardehaliH Ardehali,l sunL Sun,s shukairS Shukair,tj naikTJ Naik,f moazedF Moazed,h ardehaliH Ardehali,

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    Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Molecular and cellular biology

    VOLUME: 28

    Page Numbers: 1007-17

    Journal Abbreviation: Mol. Cell. Biol.

    ISSN: 1098-5549

    DAY: 26

    MONTH: 11

    YEAR: 2007

    Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II. Information

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    LANGUAGE: eng

    NlmUniqueID: 8109087

    Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II. Keywords Mesh Terms:

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    Grant and Affiliation Information for Glucose Phosphorylation and Mitochondrial Binding Are Required for the Protective Effects of Hexokinases I and II.

    AFFILIATION: Tarry 12-725, 303 East Chicago Ave., Chicago, IL 60611. h-ardehali@northwestern.edu.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Mol Cell Biol

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