Post-transcriptional mechanisms are responsible for the reduction in lipoprotein lipase activity in cardiomyocytes from diabetic rat hearts.
Lipoprotein lipase (LPL) activity is reduced in cardiomyocytes from rat hearts following the acute (4-5 day) induction of diabetes with 100 mg/kg streptozotocin. The molecular basis for this inhibitory effect of diabetes on LPL activity was investigated by measuring steady-state LPL mRNA content and the synthesis and turnover of LPL protein ([35S]methionine incorporation into immunoprecipitable LPL protein in pulse and pulse-chase experiments) in control and diabetic cardiomyocytes. LPL activity was reduced to approx. 50% of control in diabetic cardiomyocytes, but LPL mRNA levels and turnover (degradation) of newly synthesized LPL were unchanged. Synthesis of total protein and LPL were reduced to 72% and 71% of control respectively; therefore, relative rates of LPL synthesis were the same in control and diabetic cardiomyocytes. The diabetes-induced reduction in LPL synthesis was accompanied by a decrease in LPL mass to 78% of control, and a decrease in enzyme specific activity (0.48 to 0.33 m-unit/ng of LPL protein) since the decline in catalytic activity was greater than the decrease in LPL synthesis and mass. Thus, post-transcriptional mechanisms involving a reduction in LPL synthesis as part of a generalized decrease in total protein synthesis, together with a post-translational mechanism(s) that result in accumulation of inactive LPL protein, are responsible for the decreased LPL activity in cardiomyocytes from diabetic rat hearts.
Carroll
R
R
Medical Research Council Signal Transduction Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Liu
L
L
Severson
D L
DL
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D015536:Down-Regulation; D006321:Heart / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger; D006493:Heparin; D003513:Cycloheximide; D008071:Lipoprotein Lipase