PXD025470

PXD025470 is an original dataset announced via ProteomeXchange.

Title	Suppression of PPAR α Protects Against Hypertrophy Associated Apoptosis of the Cardiomyocytes in Mice Heart
Description	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.
HostingRepository	PRIDE
AnnounceDate	2022-04-04
AnnouncementXML	Submission_2022-04-03_18:51:27.622.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ritu Kumari
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-19 06:31:32	ID requested
⏵ 1	2022-04-03 18:51:28	announced

Kumari R, Ray AG, Mukherjee D, Chander V, Kar D, Kumar US, Bharadwaj P V P D, Banerjee SK, Konar A, Bandyopadhyay A, Mice. Front Cardiovasc Med, 9():798639(2022) [pubmed]

submitter keyword: Cardiac hypertrophy

PPAR α

apoptosis

autophagy

fenofibrate

bezafibrate

Dr. Arun Bandyopadhyay
contact affiliation	Director, CSIR-INDIAN INSTITUTE OF CHEMICAL BIOLOGY, KOLKATA,INDIA
contact email	arunb@iicb.res.in
lab head
Ritu Kumari
contact affiliation	CSIR Indian Institute of Chemical Biology
contact email	rituk2906@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD025470
     1. Label: PRIDE project
     2. Name: Suppression of PPAR α Protects Against Hypertrophy Associated Apoptosis of the Cardiomyocytes in Mice Heart