title: Post-transcriptional mechanisms are responsible for the reduction in lipoprotein lipase activity in cardiomyocytes from diabetic rat hearts.
abstract: 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.
authors.affiliation: Medical Research Council Signal Transduction Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Carroll
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: D L
authors.initials: DL
authors.lastname: Severson
mesh_terms: 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
chemical_list: D012333:RNA, Messenger; D006493:Heparin; D003513:Cycloheximide; D008071:Lipoprotein Lipase