Expression and regulation of pyruvate dehydrogenase kinase isoforms in the developing rat heart and in adulthood

Role of thyroid hormone status and lipid supply

M. C. Sugden, M. L. Langdown, Robert Harris, M. J. Holness

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Activation of the pyruvate dehydrogenase (PDH) complex (PDHC) promotes glucose disposal, whereas inactivation conserves glucose. The PDH kinases (PDHKs) regulate glucose oxidation through inhibitory phosphorylation of PDHC. The adult rat heart contains three PDHK isoforms PDHK1, PDHK2 and PDHK4. Using Western-blot analysis, with specific antibodies raised against individual recombinant PDHK1, PDHK2 and PDHK4, the present study investigated PDHK isoform expression in the developing rat heart and adulthood. We identified clear differences in the patterns of protein expression of each of these PDHK isoforms during the first 3 weeks of postnatal development, with most marked up-regulation of isoforms PDHK1 and PDHK4. Distinctions between the three cardiac PDHK isoforms were also demonstrated with respect to post-neonatal maturational up-regulation; with greatest up-regulation of PDHK1 and least up-regulation of PDHK4 from the post-neonatal period until maturity. The study also examined the role of thyroid hormone status and lipid supply on PDHK isoform expression. We observed marked selective increases in the amount of PDHK4 protein present relative to total cardiac protein in both hyperthyroidism and high-fat feeding. Overall, our data identify PDHK isoform PDHK1 as being of more potential regulatory importance for glucose oxidation in the adult compared with the neonatal heart, and cardiac PDHK4 as a PDHK isoform whose expression is specifically responsive to changes in lipid supply, suggesting that its up-regulation during early post-natal life may be the perinatal switch to use fatty acids as the energy source. We also identify regulation of pyruvate sensitivity of cardiac PDHK as a physiological variable, a change in which requires factors in addition to a change in lipid supply.

Original languageEnglish (US)
Pages (from-to)731-738
Number of pages8
JournalBiochemical Journal
Volume352
Issue number3
DOIs
StatePublished - Dec 15 2000
Externally publishedYes

Fingerprint

Thyroid Hormones
Rats
Protein Isoforms
Lipids
Up-Regulation
Glucose
Pyruvate Dehydrogenase Complex
pyruvate dehydrogenase (acetyl-transferring) kinase
Oxidation
Phosphorylation
Proteins
Hyperthyroidism
Pyruvic Acid
Fatty Acids
Western Blotting
Chemical activation
Fats
Switches
Antibodies

Keywords

  • High-fat diet
  • Hyperthyroidism
  • Pyruvate dehydrogenase complex

ASJC Scopus subject areas

  • Biochemistry

Cite this

Expression and regulation of pyruvate dehydrogenase kinase isoforms in the developing rat heart and in adulthood : Role of thyroid hormone status and lipid supply. / Sugden, M. C.; Langdown, M. L.; Harris, Robert; Holness, M. J.

In: Biochemical Journal, Vol. 352, No. 3, 15.12.2000, p. 731-738.

Research output: Contribution to journalArticle

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