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Decreased Na,K-ATPase gene expression in cardiomyopathic hamster hearts
Y Tsuruya1, U Ikeda, K Yamamoto
1Department of Cardiology, Jichi Medical School, Tochigi, Japan.
Insights
Sodium-potassium ATPase (Na,K-ATPase) mRNA and activity are significantly reduced in cardiomyopathic hamster hearts before disease onset. This suggests altered Na,K-ATPase gene expression is an early factor in cardiomyopathy development.
Area of Science:
- Cardiovascular Science
- Molecular Biology
- Genetics
Background:
- Cardiomyopathy involves heart muscle dysfunction.
- Na,K-ATPase is crucial for maintaining cardiac cell function.
- Altered gene expression may precede cardiac pathology.
Purpose of the Study:
- To investigate Na,K-ATPase mRNA expression and activity in a hamster model of cardiomyopathy.
- To determine if changes in Na,K-ATPase occur early in the disease process.
Main Methods:
- Northern blot analysis to detect Na,K-ATPase mRNA isoforms (alpha 1, 2, 3, beta 1).
- Quantitative analysis of alpha 1 subunit mRNA levels at 3 and 30 weeks.
- Enzyme activity assays on ventricular membrane fractions.
Main Results:
- Na,K-ATPase alpha 1, 2, 3, and beta 1 mRNAs were detected in both cardiomyopathic (Bio 14.6) and normal (F1b) hamsters.
- Alpha 1 subunit mRNA levels were ~50% lower in Bio 14.6 hamsters at 3 and 30 weeks.
- Na,K-ATPase activity was ~20% lower in 3-week-old Bio 14.6 hamsters.
Conclusions:
- Significantly decreased Na,K-ATPase mRNA expression and activity observed in Bio 14.6 hamsters prior to hypertrophy.
- Altered Na,K-ATPase gene expression is an early event in cardiomyopathy pathogenesis in this model.
Abstract:
We studied Na,K-ATPase mRNA expression in cardiomyopathic (Bio 14.6) and normal (F1b) Syrian hamster ventricles. In Northern blot analysis, Na,K-ATPase alpha 1, alpha 2, alpha 3 and beta 1 isoform mRNAs were detected in 3-week-old Bio 14.6 and F1b hamster ventricles. We then investigated the expression of alpha 1 subunit mRNA in Bio 14.6 hamster ventricles at the ages of 3 weeks prehypertrophic and 30 weeks hypertrophic, and in age-matched F1b hamster ventricles. The alpha 1 subunit mRNA levels in Bio 14.6 hamster ventricles were approximately 50% lower than those in F1b hamster ventricles at both 3 and 30 weeks of age. Na,K-ATPase activity measured in membrane fractions from the ventricles of 3-week-old Bio 14.6 hamsters was also approximately 20% lower than that of F1b hamsters, suggesting that the differences in the mRNA level were associated with the differences in the protein level. We conclude that Na,K-ATPase mRNA expression and enzyme activity are significantly decreased in the hearts of Bio 14.6 hamsters even before the onset of hypertrophy and cardiomyopathy, suggesting that the altered expression of Na,K-ATPase gene is an early event in the pathogenesis of cardiomyopathy in this animal model.