TAILIEUCHUNG - Báo cáo khoa học: Metabolic gene switching in the murine female heart parallels enhanced mitochondrial respiratory function in response to oxidative stress

The mechanisms underlying increased cardioprotection in younger female mice are unclear. We hypothesized that serine-threonine protein kinase (protein kinase B; Akt) triggers a metabolic gene switch (decreased fatty acids, increased glucose) in female hearts to enhance mitochondrial bio-energetic capacity, conferring protection against oxidative stress. | ễFEBS Journal Metabolic gene switching in the murine female heart parallels enhanced mitochondrial respiratory function in response to oxidative stress M. Faadiel Essop1 2 W. Y. A. Chan2 and Heinrich Taegtmeyer3 1 Department of PhysiologicalSciences Stellenbosch University South Africa 2 Hatter Heart Research Institute Faculty of Health Sciences University of Cape Town South Africa 3 Department of InternalMedicine Division of Cardiology University of Texas Houston Medical School TX USA Keywords bioenergetics cardiovascular disease gender differences gene expression mitochondrial respiration Correspondence M. F. Essop Department of Physiological Sciences Stellenbosch University Room 2009 Mike De Vries Building Merriman Avenue Stellenbosch 7600 South Africa Fax 27 21 808 3145 Tel 27 21 808 4507 E-mail mfessop@ Received 14 December 2006 revised 14 August 2007 accepted 17 August 2007 doi The mechanisms underlying increased cardioprotection in younger female mice are unclear. We hypothesized that serine-threonine protein kinase protein kinase B Akt triggers a metabolic gene switch decreased fatty acids increased glucose in female hearts to enhance mitochondrial bioenergetic capacity conferring protection against oxidative stress. Here we employed male and female control db and obese db db mice. We found diminished transcript levels of peroxisome proliferator-activated receptor-alpha muscle-type carnitine palmitoyltransferase 1 and pyruvate dehydrogenase kinase 4 in female control hearts versus male hearts. Moreover females displayed improved recovery of cardiac mitochondrial respiratory function and higher ATP levels versus males in response to acute oxygen deprivation. All these changes were reversed in female db db hearts. However we found no significant gender-based differences in levels of Akt suggesting that Akt-independent signaling mechanisms are responsible for the resilient mitochondrial phenotype observed in female .

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