Proteomics

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Suppression of PPAR α Protects Against Hypertrophy Associated Apoptosis of the Cardiomyocytes in Mice Heart


ABSTRACT: Cardiac hypertrophy is characterized by increase in the size of the cardiomyocytes which is initially triggered as an adaptive response due to various kinds of stimuli but ultimately becomes maladaptive with chronic exposure. Peroxisome proliferator activated receptor alpha (PPAR α), which is critical for mitochondrial biogenesis and fatty acid oxidation, is known to be down regulated in hypertrophied cardiomyocytes. The aim of the study was to unveil the role of PPAR α in the mechanism that drives myocardium towards maladaptation in chronic hypertrophy. Wild-type C57BL/6 and PPAR α-/- mice were subjected to isoproterenol treatment for 2 weeks (n=8). Proteomic analysis using Orbitrap mass spectrometer revealed an unexpected down regulation of apoptotic markers, Annexin V and p53. PPAR α regulated and non-regulated genes were validated using RT-PCR. Specificity for α isoform was confirmed using PPAR α agonist, fenofibrate and pan-agonist bezafibrate. Fenofibrate failed to restore PPAR α target genes, whereas bezafibrate managed to ameliorate the effects of isoproterenol for a subset of genes even in the absence of PPAR α. Autophagy markers like p62, Beclin1 and LC3 A/B were up regulated in PPAR α-/-mice therefore indicating an upsurge in autophagy. The results demonstrate hindrance to intrinsic apoptotic pathway and activation of autophagy in the absence of PPAR α in hypertrophic cardiomyocytes. Therefore, PPAR α signalling might act as a molecular switch between apoptosis and autophagy thereby playing a critical role in adaptive process in stress induced cardiomyocytes.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Heart, Electrically Active Cell

DISEASE(S): Cardiovascular System Disease

SUBMITTER: Ritu Kumari  

LAB HEAD: Dr. Arun Bandyopadhyay

PROVIDER: PXD025470 | Pride | 2022-04-04

REPOSITORIES: Pride

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Publications

Downregulation of PTEN Promotes Autophagy <i>via</i> Concurrent Reduction in Apoptosis in Cardiac Hypertrophy in PPAR α<sup>-/-</sup> Mice.

Kumari Ritu R   Ray Aleepta Guha AG   Mukherjee Dibyanti D   Chander Vivek V   Kar Dipak D   Kumar Uppulapu Shravan US   Bharadwaj P V P Deepak D   Banerjee Sanjay K SK   Konar Aditya A   Bandyopadhyay Arun A  

Frontiers in cardiovascular medicine 20220211


Cardiac hypertrophy is characterized by an increase in the size of the cardiomyocytes which is initially triggered as an adaptive response but ultimately becomes maladaptive with chronic exposure to different hypertrophic stimuli. Prolonged cardiac hypertrophy is often associated with mitochondrial dysfunctions and cardiomyocyte cell death. Peroxisome proliferator activated receptor alpha (PPAR α), which is critical for mitochondrial biogenesis and fatty acid oxidation, is down regulated in hype  ...[more]

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