Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04179 (MnSOD)
 2,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Middle-aged and old left ventricles (LVs) are structurally and functionally very similar. Compared to a young LV, both show increased wall thickness and increased cavity size, with preserved cardiac function. However, when a stressor such as myocardial infarction occurs, striking differences are revealed between young and old LVs and there is a marked reduction in survival rates for the old group. The objective of this study was to investigate the proteomic basis of age-related changes in the LV of male mice in order to identify proteins that are differentially expressed between middle-aged and old groups and to gain mechanistic insight into effects of aging on the unstressed heart. Young (3 months old; n = 6), middle-aged (MA; 15 months old; n = 6), and old (23 months old; n = 5) LVs were examined by echocardiography, homogenized, and separated into soluble and insoluble protein fractions using differential extraction. We found that the LV mass-to-tibia ratio increased from 6.4 +/- 0.2 mg/mm in young to 11.0 +/- 0.6 and 10.1 +/- 0.7 mg/mm in MA and old, respectively (both p < 0.05 vs young), which was caused by increases in both LV wall thickness and volume. Using two-dimensional gel electrophoresis, we detected age-related alterations in the levels of 73 proteins (all p < 0.05). Among these proteins were mortalin, peroxiredoxin 3, epoxide hydrolase, and the superoxide dismutases SOD-1 (Cu/ZnSOD) and SOD-2 (MnSOD), which have been previously associated with aging and/or cardiovascular disease. Together, these results reveal proteomic changes that occur in the LV with age. The proteins identified here may be useful markers of cardiac aging and may help in deducing mechanisms to explain the inability of the old heart to withstand challenge.
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PMID:The left ventricle proteome differentiates middle-aged and old left ventricles in mice. 1816 10

Biological aging is an inevitable part of life that has intrigued individuals for millennia. The progressive decline in biological systems impacts cardiac function and increases vulnerability to stress contributing to morbidity and mortality in aged individuals. Yet, our understanding of the molecular, biochemical and physiological mechanisms of aging as well as sex differences is limited. There is growing evidence indicating CYP450 epoxygenase-mediated metabolites of n-3 and n-6 polyunsaturated fatty acids (PUFAs) are active lipid mediators regulating cardiac homeostasis. These epoxy metabolites are rapidly hydrolyzed and inactivated by the soluble epoxide hydrolase (sEH). The current study characterized cardiac function in young and aged sEH null mice compared to the corresponding wild-type (WT) mice. All aged mice had significantly increased cardiac hypertrophy, except in aged female sEH null mice. Cardiac function as assessed by echocardiography demonstrated a marked decline in aged WT mice, notably significant decreases in ejection fraction and fractional shortening in both sexes. Interestingly, aged female sEH null mice had preserved systolic function, while aged male sEH null mice had preserved diastolic function compared to aged WT mice. Assessment of cardiac mitochondria demonstrated an increased expression of acetyl Mn-SOD levels that correlated with decreased Sirt-3 activity in aged WT males and females. Conversely, aged sEH null mice had preserved Sirt-3 activity and better mitochondrial ultrastructure compared to WT mice. Consistent with these changes, the activity level of SOD significantly decreased in WT animals but was preserved in aged sEH null animals. Markers of oxidative stress demonstrated age-related increase in protein carbonyl levels in WT and sEH null male mice. Together, these data highlight novel cardiac phenotypes from sEH null mice demonstrating a sexual dimorphic pattern of aging in the heart.
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PMID:Age and Sex Differences in Hearts of Soluble Epoxide Hydrolase Null Mice. 3211 60