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. 1995 Aug 15;310(Pt 1):67–72. doi: 10.1042/bj3100067

Post-transcriptional mechanisms are responsible for the reduction in lipoprotein lipase activity in cardiomyocytes from diabetic rat hearts.

R Carroll 1, L Liu 1, D L Severson 1
PMCID: PMC1135855  PMID: 7646474

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.

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Selected References

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