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Multiple cardiac contractile protein abnormalities in myopathic Syrian hamsters (BIO 53 : 58)
Insights
Cardiac myofibrillar ATPase activity is altered in myopathic hamsters, with changes in myosin isoenzymes appearing later in disease progression. These findings highlight stage-specific alterations in contractile proteins during myopathy development.
Area of Science:
- Biochemistry
- Cardiology
- Molecular Biology
Background:
- Genetic myopathy in hamsters affects cardiac function.
- Understanding alterations in cardiac contractile proteins is crucial for myopathy research.
Purpose of the Study:
- To investigate the time course of changes in cardiac myofibrillar ATPase activity and myosin isoenzyme distribution in genetically myopathic hamsters.
- To evaluate the relationship between myofibrillar ATPase activity and free calcium concentration.
Main Methods:
- Studied cardiac myofibrils from myopathic hamsters at various ages (1 to 7 months).
- Assessed Mg2+-Ca2+ ATPase activity, myosin ATPase activity, and actin-activated Mg2+-ATPase activity.
- Analyzed cardiac myosin isoenzyme distribution using SDS-PAGE.
Main Results:
- Elevated Mg2+-Ca2+ ATPase activity was observed as early as 2 months in myopathic hamsters, increasing further by 4-7 months.
- Myosin Ca2+ ATPase and actin-activated Mg2+-ATPase activities decreased significantly in myopathic hearts at 4-7 months.
- Myosin isoenzyme distribution shifted from V1 predominance to V1=V3 and then V3 predominance in myopathics by 4-7 months.
Conclusions:
- Cardiac contractile protein alterations occur at different stages of hamster genetic myopathy.
- Changes in ATPase activities and myosin isoenzyme profiles indicate progressive myopathic changes.
- The regulation of myofibrillar assembly by calcium remained intact despite ATPase alterations.
Abstract:
Hearts of genetically myopathic male hamsters (BIO 53 : 58) were studied at 1 month, 2 months, 3 months, 4 to 5 months and 7 months of age. The time course of alterations in the cardiac myofibrillar ATPase activity, the relationship of myofibrillar ATPase activity to free [Ca2+], myosin ATPase activity and the distribution of heavy chain myosin isoenzymes were evaluated. Mg2+-Ca2+ ATPase activity of cardiac myofibrils in myopathics was increased in 4 month and 7 month-old hamsters. Elevated Mg2+ ATPase activity was found as early as in 2-month-old hamster. However, there was no loss in the regulation of the myopathic myofibrillar assembly as measured by the PCa response (10(-7) M to 10(-4) M Ca2+). Scans of SDS electrophoresis slab gels of cardiac myofibrillar proteins from control (C) and myopathic animals (M) did not show any differences at any age group (1, 4 and 7 months). There was a significant decrease in myosin Ca2+ ATPase activity and actin activated Mg2+-ATPase activity at 4 to 5 months and 7 months of age in the myopathic hearts. At all ages in normal and myopathic animals cardiac myosin consisted of three isoenzymes, V1, V2 and V3. At all ages in controls and at 1 to 3 months in myopathics, V1 predominated and the isoenzyme distribution was V1 greater than V2 greater than V3. However, in myopathics at 4 to 5 months, the distribution was V1 = V3 greater than V2 and at 7 months was V3 greater than V2 greater than V1. Our experiments suggest alterations in different components of the contractile protein system that occur at different stages of myopathy.