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Sarcoplasmic reticulum dysfunction: phospholipid alterations induced by lysosomal phospholipase C.
The American Journal of Physiology
|November 1, 1986
Summary
Myocardial ischemia disrupts cardiac function via oxygen free radicals activating phospholipase C, impairing calcium transport. Antioxidant treatment with superoxide dismutase and catalase protected against this damage.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Cellular Biology
Background:
- Myocardial ischemia disrupts cardiac excitation-contraction coupling, linked to lysosomal activation.
- Oxygen free radicals are hypothesized to mediate lysosomal activation during ischemia.
Purpose of the Study:
- To test if myocardial ischemia activates lysosomal phospholipase C and disrupts sarcoplasmic reticulum (SR) calcium transport via oxygen free radicals.
- To investigate the protective effects of antioxidants against ischemia-induced SR dysfunction.
Main Methods:
- Studied three groups of dogs: controls, ischemic, and ischemic pretreated with superoxide dismutase (SOD) and catalase.
- Assessed in vitro isolated SR calcium uptake rates and Ca2+-stimulated ATPase activity.
- Analyzed SR sphingomyelinase-phospholipase C (SM-PLC) activity and phospholipid composition.
Main Results:
- Ischemia significantly depressed SR calcium uptake and ATPase activity, particularly at acidic pH.
- Pretreatment with SOD and catalase inhibited the depression of SR function.
- Ischemia decreased SM-PLC activity in SR, while controls showed acid-activated SM-PLC.
Conclusions:
- Oxygen free radicals mediate ischemia-induced activation of phospholipase C and disruption of SR calcium transport.
- Antioxidant pretreatment with SOD and catalase protects against these functional deficits.
- Lysosomal enzyme activation plays a role in the pathophysiology of myocardial ischemia.