PMID- 35224041
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220301
IS  - 2297-055X (Print)
IS  - 2297-055X (Electronic)
IS  - 2297-055X (Linking)
VI  - 9
DP  - 2022
TI  - Downregulation of PTEN Promotes Autophagy via Concurrent Reduction in Apoptosis 
      in Cardiac Hypertrophy in PPAR alpha(-/-) Mice.
PG  - 798639
LID - 10.3389/fcvm.2022.798639 [doi]
LID - 798639
AB  - 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 alpha), which is critical for mitochondrial biogenesis and fatty 
      acid oxidation, is down regulated in hypertrophied cardiomyocytes. Yet, the role 
      of PPAR alpha in cardiomyocyte death is largely unknown. To assess the role of PPAR alpha 
      in chronic hypertrophy, isoproterenol, a beta-adrenergic receptor agonist was 
      administered in PPAR alpha knock out (PPAR alpha(-/-)) mice for 2 weeks and hypertrophy 
      associated changes in cardiac tissues were observed. Echocardiographic analysis 
      ensured the development of cardiac hypertrophy and compromised hemodynamics in 
      PPAR alpha(-/-) mice. Proteomic analysis using high resolution mass spectrometer 
      identified about 1,200 proteins enriched in heart tissue. Proteins were 
      classified according to biological pathway and molecular functions. We observed 
      an unexpected down regulation of apoptotic markers, Annexin V and p53 in 
      hypertrophied heart tissue. Further validation revealed a significant down 
      regulation of apoptosis regulator, PTEN, along with other apoptosis markers like 
      p53, Caspase 9 and c-PARP. The autophagy markers Atg3, Atg5, Atg7, p62, Beclin1 
      and LC3 A/B were up regulated in PPAR alpha(-/-) mice indicating an increase in 
      autophagy. Similar observations were made in a high cholesterol diet fed PPAR 
      alpha(-/-)mice. The results were further validated in vitro using NRVMs and H9C2 cell 
      line by blocking PPAR alpha that resulted in enhanced autophagosome formation upon 
      hypertrophic stimulation. The results demonstrate that in the absence of PPAR alpha 
      apoptotic pathway is inhibited while autophagy is enhanced. The data suggest that 
      PPAR alpha signaling might act as a molecular switch between apoptosis and autophagy 
      thereby playing a critical role in adaptive process in cardiac hypertrophy.
CI  - Copyright (c) 2022 Kumari, Ray, Mukherjee, Chander, Kar, Kumar, Bharadwaj P.V.P., 
      Banerjee, Konar and Bandyopadhyay.
FAU - Kumari, Ritu
AU  - Kumari R
AD  - Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 
      Kolkata, India.
FAU - Ray, Aleepta Guha
AU  - Ray AG
AD  - Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 
      Kolkata, India.
FAU - Mukherjee, Dibyanti
AU  - Mukherjee D
AD  - Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 
      Kolkata, India.
FAU - Chander, Vivek
AU  - Chander V
AD  - Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 
      Kolkata, India.
FAU - Kar, Dipak
AU  - Kar D
AD  - Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 
      Kolkata, India.
FAU - Kumar, Uppulapu Shravan
AU  - Kumar US
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      Research, Guwahati, India.
FAU - Bharadwaj P V P, Deepak
AU  - Bharadwaj P V P D
AD  - Department of Pharmacology and Toxicology, National Institute of Pharmaceutical 
      Education and Research, Guwahati, India.
FAU - Banerjee, Sanjay K
AU  - Banerjee SK
AD  - Department of Biotechnology, National Institute of Pharmaceutical Education and 
      Research, Guwahati, India.
FAU - Konar, Aditya
AU  - Konar A
AD  - Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 
      Kolkata, India.
FAU - Bandyopadhyay, Arun
AU  - Bandyopadhyay A
AD  - Cell Biology and Physiology Division, CSIR-Indian Institute of Chemical Biology, 
      Kolkata, India.
LA  - eng
PT  - Journal Article
DEP - 20220211
PL  - Switzerland
TA  - Front Cardiovasc Med
JT  - Frontiers in cardiovascular medicine
JID - 101653388
PMC - PMC8881053
OTO - NOTNLM
OT  - PPAR alpha
OT  - PTEN
OT  - apoptosis
OT  - autophagy
OT  - cardiac hypertrophy
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/03/01 06:00
MHDA- 2022/03/01 06:01
PMCR- 2022/01/01
CRDT- 2022/02/28 05:40
PHST- 2021/10/20 00:00 [received]
PHST- 2022/01/14 00:00 [accepted]
PHST- 2022/02/28 05:40 [entrez]
PHST- 2022/03/01 06:00 [pubmed]
PHST- 2022/03/01 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcvm.2022.798639 [doi]
PST - epublish
SO  - Front Cardiovasc Med. 2022 Feb 11;9:798639. doi: 10.3389/fcvm.2022.798639. 
      eCollection 2022.