PMID- 25826393
OWN - NLM
STAT- MEDLINE
DCOM- 20160321
LR  - 20201209
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 3
DP  - 2015
TI  - Pik3ip1 modulates cardiac hypertrophy by inhibiting PI3K pathway.
PG  - e0122251
LID - 10.1371/journal.pone.0122251 [doi]
LID - e0122251
AB  - Cardiac hypertrophy is an adaptive response to various physiological and 
      pathological stimuli. Phosphoinositide-3 kinase (PI3K) is a highly conserved 
      lipid kinase involved in physiological cardiac hypertrophy (PHH). PI3K 
      interacting protein1 (Pik3ip1) shares homology with the p85 regulatory subunit of 
      PI3K and is known to interact with the p110 catalytic subunit of PI3K, leading to 
      attenuation of PI3K activity in liver and immune cells. However, the role of 
      Pik3ip1 in the heart remains unknown. In the present study, the effects of 
      Pik3ip1 on cardiac hypertrophy were examined. We found that the expression level 
      of Pik3ip1 was markedly higher in cardiomyocytes than in fibroblasts. The 
      interaction of Pik3ip1 with the p110a subunit of PI3K in the heart was identified 
      by immunoprecipitation using neonatal rat cardiomyocytes (NRCM). Approximately 
      35% knockdown of Pik3ip1 was sufficient to induce myocardial hypertrophy. Pik3ip1 
      deficiency was shown to lead to activation of PI3K/protein kinase B (AKT)/ 
      mammalian target of rapamycin (mTOR) signaling pathway, increasing protein 
      synthesis and cell size. However, adenovirus-mediated overexpression of Pik3ip1 
      attenuated PI3K-mediated cardiac hypertrophy. Pik3ip1 was upregulated by PHH due 
      to swimming training, but not by pathological cardiac hypertrophy (PAH) due to 
      pressure-overload, suggesting that Pik3ip1 plays a compensatory negative role for 
      PHH. Collectively, our results elucidate the mechanisms for the roles of Pik3ip1 
      in PI3K/AKT signaling pathway.
FAU - Song, Hong Ki
AU  - Song HK
AD  - School of Life Sciences and Systems Biology Research Center, Gwangju Institute of 
      Science and Technology (GIST), Gwangju, Republic of Korea.
FAU - Kim, Jiyeon
AU  - Kim J
AD  - School of Life Sciences and Systems Biology Research Center, Gwangju Institute of 
      Science and Technology (GIST), Gwangju, Republic of Korea.
FAU - Lee, Jong Sub
AU  - Lee JS
AD  - School of Life Sciences and Systems Biology Research Center, Gwangju Institute of 
      Science and Technology (GIST), Gwangju, Republic of Korea.
FAU - Nho, Kyoung Jin
AU  - Nho KJ
AD  - School of Life Sciences and Systems Biology Research Center, Gwangju Institute of 
      Science and Technology (GIST), Gwangju, Republic of Korea.
FAU - Jeong, Hae Chang
AU  - Jeong HC
AD  - Department of Cardiology, Chonnam National University Hospital, Gwangju, Republic 
      of Korea.
FAU - Kim, Jihwa
AU  - Kim J
AD  - School of Life Sciences and Systems Biology Research Center, Gwangju Institute of 
      Science and Technology (GIST), Gwangju, Republic of Korea.
FAU - Ahn, Youngkeun
AU  - Ahn Y
AD  - Department of Cardiology, Chonnam National University Hospital, Gwangju, Republic 
      of Korea.
FAU - Park, Woo Jin
AU  - Park WJ
AD  - School of Life Sciences and Systems Biology Research Center, Gwangju Institute of 
      Science and Technology (GIST), Gwangju, Republic of Korea.
FAU - Kim, Do Han
AU  - Kim DH
AD  - School of Life Sciences and Systems Biology Research Center, Gwangju Institute of 
      Science and Technology (GIST), Gwangju, Republic of Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150331
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Pik3ip1 protein, mouse)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.1.137 (1-phosphatidylinositol 3-kinase p110 subunit, mouse)
RN  - EC 2.7.1.137 (Class I Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Cardiomegaly/enzymology/metabolism/*prevention & control
MH  - Carrier Proteins/genetics/*physiology
MH  - Cells, Cultured
MH  - Class I Phosphatidylinositol 3-Kinases/metabolism
MH  - Gene Silencing
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Membrane Proteins
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocytes, Cardiac/cytology/enzymology/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Physical Conditioning, Animal
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC4380398
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/04/01 06:00
MHDA- 2016/03/22 06:00
PMCR- 2015/03/31
CRDT- 2015/04/01 06:00
PHST- 2014/10/15 00:00 [received]
PHST- 2015/02/10 00:00 [accepted]
PHST- 2015/04/01 06:00 [entrez]
PHST- 2015/04/01 06:00 [pubmed]
PHST- 2016/03/22 06:00 [medline]
PHST- 2015/03/31 00:00 [pmc-release]
AID - PONE-D-14-45905 [pii]
AID - 10.1371/journal.pone.0122251 [doi]
PST - epublish
SO  - PLoS One. 2015 Mar 31;10(3):e0122251. doi: 10.1371/journal.pone.0122251. 
      eCollection 2015.