Key regulators of mitochondrial biogenesis are increased in kidneys of growth hormone receptor knockout (GHRKO) mice

    Authors

    A. Gesing; A. Bartke; F. Y. Wang; M. Karbownik-Lewinska;M. M. Masternak

    Comments

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    Abbreviated Journal Title

    Cell Biochem. Funct.

    Keywords

    mitochondrial biogenesis; growth hormone receptor knockout (GHRKO) mice; skeletal muscles; kidneys; proteins; calorie restriction; visceral fat; NITRIC-OXIDE SYNTHASE; GENE-DISRUPTED MICE; CALORIE RESTRICTION; SKELETAL-MUSCLE; INSULIN-RESISTANCE; TARGETED DISRUPTION; ENERGY-METABOLISM; LARON-SYNDROME; PROTEIN GENE; LIFE-SPAN; Biochemistry & Molecular Biology; Cell Biology

    Abstract

    The growth hormone receptor knockout (GHRKO) mice are remarkably long-lived and highly insulin sensitive. Alterations in mitochondrial biogenesis are associated with aging and various metabolic derangements. We have previously demonstrated increased gene expression of key regulators of mitochondriogenesis in kidneys, hearts and skeletal muscles of GHRKO mice. The aim of the present study was to quantify the protein levels of the following regulators of mitochondriogenesis: peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), AMP-activated protein kinase alpha (AMPK alpha), phospho-AMPK alpha (p-AMPK alpha), sirtuin-3 (SIRT-3), endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), nuclear respiratory factor-1 (NRF-1) and mitofusin-2 (MFN-2) in skeletal muscles and kidneys of GHRKOs in comparison to normal mice. We also were interested in the effects of calorie restriction (CR) and visceral fat removal (VFR) on these parameters. Both CR and VFR improve insulin sensitivity and can extend life span. Results: The renal levels of PGC-1 alpha, AMPK alpha, p-AMPK alpha, SIRT-3, eNOS, p-eNOS and MFN-2 were increased in GHRKOs. In the GHRKO skeletal muscles, only MFN-2 was increased. Levels of the examined proteins were not affected by CR (except for PGC-1 alpha and p-eNOS in skeletal muscles) or VFR. Conclusion: GHRKO mice have increased renal protein levels of key regulators of mitochondriogenesis, and this may contribute to increased longevity of these knockouts. Copyright (C) 2011 John Wiley & Sons, Ltd.

    Journal Title

    Cell Biochemistry and Function

    Volume

    29

    Issue/Number

    6

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    459

    Last Page

    467

    WOS Identifier

    WOS:000294267100004

    ISSN

    0263-6484

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