Starvation and diabetes increase the amount of pyruvate dehydrogenase kinase isoenzyme 4 in rat heart.
This study investigated whether conditions known to alter the activity and phosphorylation state of the pyruvate dehydrogenase complex have specific effects on the levels of isoenzymes of pyruvate dehydrogenase kinase (PDK) in rat heart. Immunoblot analysis revealed a remarkable increase in the amount of PDK4 in the hearts of rats that had been starved or rendered diabetic with streptozotocin. Re-feeding of starved rats and insulin treatment of diabetic rats very effectively reversed the increase in PDK4 protein and restored PDK enzyme activity to levels of chow-fed control rats. Starvation and diabetes also markedly increased the abundance of PDK4 mRNA, and re-feeding and insulin treatment reduced levels of the message to that of controls. In contrast with the findings for PDK4, little or no changes in the amounts of PDK1 and PDK2 protein and the abundance of their messages occurred in response to starvation and diabetes. The observed shift in the relative abundance of PDK isoenzymes probably explains previous studies of the effects of starvation and diabetes on heart PDK activity. The results indicate that control of the amount of PDK4 is important in long-term regulation of the activity of the pyruvate dehydrogenase complex in rat heart.
Wu
P
P
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202-5122, USA.
Sato
J
J
Zhao
Y
Y
Jaskiewicz
J
J
Popov
K M
KM
Harris
R A
RA
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013217:Starvation; D013997:Time Factors
D007328:Insulin; D007527:Isoenzymes; C000631434:Pdk1 protein, rat; C000631436:Pdk2 protein, rat; C000631440:Pdk4 protein, rat; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; D012333:RNA, Messenger; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases