ABSTRACT
Calorie restriction (CR) improved health span in 2 longitudinal studies in nonhuman primates (NHPs), yet only the University of Wisconsin (UW) study demonstrated an increase in survival in CR monkeys relative to controls; the National Institute on Aging (NIA) study did not. Here, analysis of left ventricle samples showed that CR did not reduce cardiac fibrosis relative to controls. However, there was a 5.9-fold increase of total fibrosis in UW hearts, compared with NIA hearts. Diet composition was a prominent difference between the studies; therefore, we used the NHP diets to characterize diet-associated molecular and functional changes in the hearts of mice. Consistent with the findings from the NHP samples, mice fed a UW or a modified NIA diet with increased sucrose and fat developed greater cardiac fibrosis compared with mice fed the NIA diet, and transcriptomics analysis revealed diet-induced activation of myocardial oxidative phosphorylation and cardiac muscle contraction pathways.
Subject(s)
Dietary Fats/adverse effects , Dietary Sucrose/adverse effects , Heart/physiopathology , Myocardial Contraction/physiology , Myocardium/pathology , Adolescent , Age Factors , Aged , Aging/physiology , Animals , Caloric Restriction , Child , Disease Models, Animal , Female , Fibrosis , Heart Ventricles/pathology , Humans , Macaca mulatta , Male , Mice , Oxidative Phosphorylation , Species Specificity , Young AdultABSTRACT
Bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. The human pathogen Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, utilizes the transcriptional regulator OxyR to activate genes related to oxidative stress resistance, including peroxiredoxin PrxA, in response to hydrogen peroxide. In this study, we identified another OxyR homolog in V. cholerae, which we named OxyR2, and we renamed the previous OxyR OxyR1. We found that OxyR2 is required to activate its divergently transcribed gene ahpC, encoding an alkylhydroperoxide reductase, independently of H2O2 A conserved cysteine residue in OxyR2 is critical for this function. Mutation of either oxyR2 or ahpC rendered V. cholerae more resistant to H2O2 RNA sequencing analyses indicated that OxyR1-activated oxidative stress-resistant genes were highly expressed in oxyR2 mutants even in the absence of H2O2 Further genetic analyses suggest that OxyR2-activated AhpC modulates OxyR1 activity by maintaining low intracellular concentrations of H2O2 Furthermore, we showed that ΔoxyR2 and ΔahpC mutants were less fit when anaerobically grown bacteria were exposed to low levels of H2O2 or incubated in seawater. These results suggest that OxyR2 and AhpC play important roles in the V. cholerae oxidative stress response.
