A PKM2 signature in the failing heart.

Autor: Rees ML; Department of Internal Medicine, Division of Cardiology, The University of Texas Medical School at Houston, 6431 Fannin Street, MSB 1.220, Houston, TX 77030, USA., Subramaniam J; Department of Internal Medicine, Division of Cardiology, The University of Texas Medical School at Houston, 6431 Fannin Street, MSB 1.220, Houston, TX 77030, USA., Li Y; Department of Internal Medicine, Division of Cardiology, The University of Texas Medical School at Houston, 6431 Fannin Street, MSB 1.220, Houston, TX 77030, USA., Hamilton DJ; Department of Medicine, Division of Endocrinology, Bioenergetic Laboratory, Houston Methodist Research Institute, 6550 Fannin Street, #1001, Houston, TX 77030, USA., Frazier OH; Texas Heart Institute, CHI St. Luke's Health - Baylor St. Luke's Medical Center, MC 2-114A, PO Box 20345, Houston, TX 77225, USA., Taegtmeyer H; Department of Internal Medicine, Division of Cardiology, The University of Texas Medical School at Houston, 6431 Fannin Street, MSB 1.220, Houston, TX 77030, USA; Texas Heart Institute, CHI St. Luke's Health - Baylor St. Luke's Medical Center, MC 2-114A, PO Box 20345, Houston, TX 77225, USA. Electronic address: Heinrich.Taegtmeyer@uth.tmc.edu.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2015 Apr 10; Vol. 459 (3), pp. 430-6. Date of Electronic Publication: 2015 Feb 28.
DOI: 10.1016/j.bbrc.2015.02.122
Abstrakt: A salient feature of the failing heart is metabolic remodeling towards predominant glucose metabolism and activation of the fetal gene program. Sunitinib is a multitargeted receptor tyrosine kinase inhibitor used for the treatment of highly vascularized tumors. In diabetic patients, sunitinib significantly decreases blood glucose. However, a considerable proportion of sunitinib-treated patients develop cardiac dysfunction or failure. We asked whether sunitinib treatment results in shift towards glycolysis in the heart. Glucose uptake by the heart was increased fivefold in mice treated with sunitinib. Transcript analysis by qPCR revealed an induction of genes associated with glycolysis and reactivation of the fetal gene program. Additionally, we observed a shift in the enzyme pyruvate kinase from the adult M1 (PKM1) isoform to the fetal M2 (PKM2) isoform, a hallmark of the Warburg Effect. This novel observation led us to examine whether a similar shift occurs in human heart failure. Examination of tissue from patients with heart failure similarly displayed an induction of PKM2. Moreover, this phenomenon was partially reversed following mechanical unloading. We propose that pyruvate kinase isoform switching represents a novel feature of the fetal gene program in the failing heart.
(Published by Elsevier Inc.)
Databáze: MEDLINE
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