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Pik3ip1 modulates cardiac hypertrophy by inhibiting PI3K pathway.

Song HK, Kim J, Lee JS, Nho KJ, Jeong HC, Kim J, Ahn Y, Park WJ, Kim do H - PLoS ONE (2015)

Bottom Line: We found that the expression level of Pik3ip1 was markedly higher in cardiomyocytes than in fibroblasts.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.Collectively, our results elucidate the mechanisms for the roles of Pik3ip1 in PI3K/AKT signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Pik3ip1 is enriched in neonatal rat ventricular cardiomyocytes and interacts with p110α.(A) mRNA levels of Pik3ip1 were measured in cardiomyocytes (CMs) and fibroblasts (FBs) using quantitative reverse transcription PCR (qRT-PCR) (n = 3, * p < 0.05, t test). (B) Western blot analysis was performed to compare CMs and FBs using anti-Pik3ip1, Vimentin, and α-actinin antibodies. (C, D) The interaction between Pik3ip1 and p110α was analyzed in adult mouse heart tissue (C) and NRCMs (D) using anti-p110α or anti-Pik3ip1 antibodies.
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pone.0122251.g001: Pik3ip1 is enriched in neonatal rat ventricular cardiomyocytes and interacts with p110α.(A) mRNA levels of Pik3ip1 were measured in cardiomyocytes (CMs) and fibroblasts (FBs) using quantitative reverse transcription PCR (qRT-PCR) (n = 3, * p < 0.05, t test). (B) Western blot analysis was performed to compare CMs and FBs using anti-Pik3ip1, Vimentin, and α-actinin antibodies. (C, D) The interaction between Pik3ip1 and p110α was analyzed in adult mouse heart tissue (C) and NRCMs (D) using anti-p110α or anti-Pik3ip1 antibodies.

Mentions: Because Pik3ip is known to be expressed in mouse heart tissue [8], Pik3ip expression was examined in two cardiac cell types, cardiomyocytes and fibroblasts, using neonatal rat heart. The results showed that Pik3ip1 was enriched in cardiomyocytes, but not in fibroblasts, at both the mRNA and protein levels (Fig 1A and 1B). The validities of the two cardiac fractions were confirmed by examining the expression levels of α-actinin (Actn1), a myocyte-specific protein [16], and vimentin (Vim), a fibroblast-specific protein [17]. Fig. A in S1 File show that Actn1 and Vim were significantly enriched in the cardiomyocyte and fibroblast fractions, respectively.


Pik3ip1 modulates cardiac hypertrophy by inhibiting PI3K pathway.

Song HK, Kim J, Lee JS, Nho KJ, Jeong HC, Kim J, Ahn Y, Park WJ, Kim do H - PLoS ONE (2015)

Pik3ip1 is enriched in neonatal rat ventricular cardiomyocytes and interacts with p110α.(A) mRNA levels of Pik3ip1 were measured in cardiomyocytes (CMs) and fibroblasts (FBs) using quantitative reverse transcription PCR (qRT-PCR) (n = 3, * p < 0.05, t test). (B) Western blot analysis was performed to compare CMs and FBs using anti-Pik3ip1, Vimentin, and α-actinin antibodies. (C, D) The interaction between Pik3ip1 and p110α was analyzed in adult mouse heart tissue (C) and NRCMs (D) using anti-p110α or anti-Pik3ip1 antibodies.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380398&req=5

pone.0122251.g001: Pik3ip1 is enriched in neonatal rat ventricular cardiomyocytes and interacts with p110α.(A) mRNA levels of Pik3ip1 were measured in cardiomyocytes (CMs) and fibroblasts (FBs) using quantitative reverse transcription PCR (qRT-PCR) (n = 3, * p < 0.05, t test). (B) Western blot analysis was performed to compare CMs and FBs using anti-Pik3ip1, Vimentin, and α-actinin antibodies. (C, D) The interaction between Pik3ip1 and p110α was analyzed in adult mouse heart tissue (C) and NRCMs (D) using anti-p110α or anti-Pik3ip1 antibodies.
Mentions: Because Pik3ip is known to be expressed in mouse heart tissue [8], Pik3ip expression was examined in two cardiac cell types, cardiomyocytes and fibroblasts, using neonatal rat heart. The results showed that Pik3ip1 was enriched in cardiomyocytes, but not in fibroblasts, at both the mRNA and protein levels (Fig 1A and 1B). The validities of the two cardiac fractions were confirmed by examining the expression levels of α-actinin (Actn1), a myocyte-specific protein [16], and vimentin (Vim), a fibroblast-specific protein [17]. Fig. A in S1 File show that Actn1 and Vim were significantly enriched in the cardiomyocyte and fibroblast fractions, respectively.

Bottom Line: We found that the expression level of Pik3ip1 was markedly higher in cardiomyocytes than in fibroblasts.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.Collectively, our results elucidate the mechanisms for the roles of Pik3ip1 in PI3K/AKT signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus