UNLABELLED: 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 γ co-activator 1α (PGC-1α), AMP-activated protein kinase α (AMPKα), phospho-AMPKα (p-AMPKα), 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-1α, AMPKα, p-AMPKα, 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-1α 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.
UNLABELLED: 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 γ co-activator 1α (PGC-1α), AMP-activated protein kinase α (AMPKα), phospho-AMPKα (p-AMPKα), 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-1α, AMPKα, p-AMPKα, 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-1α 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.
Authors: Y Zhou; B C Xu; H G Maheshwari; L He; M Reed; M Lozykowski; S Okada; L Cataldo; K Coschigamo; T E Wagner; G Baumann; J J Kopchick Journal: Proc Natl Acad Sci U S A Date: 1997-11-25 Impact factor: 11.205
Authors: H Duplain; R Burcelin; C Sartori; S Cook; M Egli; M Lepori; P Vollenweider; T Pedrazzini; P Nicod; B Thorens; U Scherrer Journal: Circulation Date: 2001-07-17 Impact factor: 29.690
Authors: Adam Gesing; Michal M Masternak; Feiya Wang; Andrzej Lewinski; Malgorzata Karbownik-Lewinska; Andrzej Bartke Journal: Exp Biol Med (Maywood) Date: 2011-02
Authors: Hsiuchen Chen; Marc Vermulst; Yun E Wang; Anne Chomyn; Tomas A Prolla; J Michael McCaffery; David C Chan Journal: Cell Date: 2010-04-16 Impact factor: 41.582
Authors: Anthony E Civitarese; Stacy Carling; Leonie K Heilbronn; Mathew H Hulver; Barbara Ukropcova; Walter A Deutsch; Steven R Smith; Eric Ravussin Journal: PLoS Med Date: 2007-03 Impact factor: 11.069
Authors: Zhongbo Liu; Maria E Solesio; Mitchell B Schaffler; Dorra Frikha-Benayed; Clifford J Rosen; Haim Werner; John J Kopchick; Evgeny V Pavlov; Andrey Y Abramov; Shoshana Yakar Journal: J Bone Miner Res Date: 2018-09-14 Impact factor: 6.741
Authors: Svetlana Ukraintseva; Konstantin Arbeev; Matt Duan; Igor Akushevich; Alexander Kulminski; Eric Stallard; Anatoliy Yashin Journal: Mech Ageing Dev Date: 2020-12-16 Impact factor: 5.432
Authors: Adam Gesing; Feiya Wang; Edward O List; Darlene E Berryman; Michal M Masternak; Andrzej Lewinski; Malgorzata Karbownik-Lewinska; John J Kopchick; Andrzej Bartke Journal: J Gerontol A Biol Sci Med Sci Date: 2014-02-18 Impact factor: 6.053
Authors: Katarzyna Piotrowska; Sylwia J Borkowska; Barbara Wiszniewska; Maria Laszczyńska; Sylwia Słuczanowska-Głabowska; Aaron M Havens; John J Kopchick; Andrzej Bartke; Russel S Taichman; Magda Kucia; Mariusz Z Ratajczak Journal: Histol Histopathol Date: 2013-04-24 Impact factor: 2.303
Authors: Adam Gesing; Michal M Masternak; Andrzej Lewinski; Malgorzata Karbownik-Lewinska; John J Kopchick; Andrzej Bartke Journal: J Gerontol A Biol Sci Med Sci Date: 2012-11-29 Impact factor: 6.053
Authors: Ilona Zawada; Michal M Masternak; Edward O List; Michael B Stout; Darlene E Berryman; Andrzej Lewinski; John J Kopchick; Andrzej Bartke; Malgorzata Karbownik-Lewinska; Adam Gesing Journal: Aging (Albany NY) Date: 2015-03 Impact factor: 5.682