ATM deficiency differentially affects expression of proteins related to fatty acid oxidation and oxidative stress in a sex-specific manner in response to Western-type diet prior to and following myocardial infarction
Published work has shown that ataxia-telangiectasia mutated kinase (ATM) deficiency is associated with cardioprotective effects in Western-type diet (WD)-fed female mice. This study assessed the expression of proteins related to fatty acid oxidation (FAO) and oxidative stress in WD-fed male and fema...
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Veröffentlicht in: | Life sciences (1973) 2024-04, Vol.342, p.122541-122541, Article 122541 |
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Zusammenfassung: | Published work has shown that ataxia-telangiectasia mutated kinase (ATM) deficiency is associated with cardioprotective effects in Western-type diet (WD)-fed female mice. This study assessed the expression of proteins related to fatty acid oxidation (FAO) and oxidative stress in WD-fed male and female mouse hearts, and investigated if sex-specific cardioprotective effects in WD-fed female ATM-deficient mice are maintained following myocardial infarction (MI).
Wild-type (WT) and ATM-deficient (hKO) mice (both sexes) were placed on WD for 14 weeks. Myocardial tissue from a subset of mice was used for western blot analyses, while another subset of WD-fed mice underwent MI. Heart function was analyzed by echocardiography prior to and 1 day post-MI.
CPT1B (mitochondrial FAO enzyme) expression was lower in male hKO-WD, while it was higher in female hKO-WD vs WT-WD. WD-mediated decrease in ACOX1 (peroxisomal FAO enzyme) expression was only observed in male WT-WD. PMP70 (transports fatty acyl-CoA across peroxisomal membrane) expression was lower in male hKO-WD vs WT-WD. Catalase (antioxidant enzyme) expression was higher, while Nox4 (pro-oxidant enzyme) expression was lower in female hKO-WD vs WT-WD. Heart function was better in female hKO-WD vs WT-WD. However, post-MI heart function was not significantly different among all MI groups. Post-MI, CPT1B and catalase expression was higher in male hKO-WD-MI vs WT-WD-MI, while Nox4 expression was higher in female hKO-WD-MI vs WT-WD-MI.
Increased mitochondrial FAO and decreased oxidative stress contribute towards ATM deficiency-mediated cardioprotective effects in WD-fed female mice which are abolished post-MI with increased Nox4 expression. |
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ISSN: | 0024-3205 1879-0631 |
DOI: | 10.1016/j.lfs.2024.122541 |