Regulation of Myocardial Contractility and Cell Size by Distinct PI3K-PTEN Signaling Pathways

Crackower, Michael A.; Oudit, Gavin Y.; Kozieradzki, I.; Sarao, Renu; Sun, Hui; Sasaki, Takehiko; Hirsch, Emilio; Suzuki, Akira; Shioi, Tetsuo; Irie-Sasaki, Junko; Sah, Rajan; Cheng, Hai; Rybin, Vitalyi O.; Lembo, Giuseppe; Fratta, Luigi; Oliveira-dos-Santos, Antonio J.; Benovic, J. L.; Kahn, C. Ronald; Izumo, Seigo; Steinberg, Susan F.; Wymann, Matthias P.; Backx, Peter H.; Penninger, Josef

doi:10.1016/s0092-8674(02)00969-8

Cited by 545 publications

(568 citation statements)

References 45 publications

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“…The heart expresses three major Class 1 PI3K isoforms -PI3K, PI3K and PI3K (Crackower et al, 2002). Class IA and IB PI3Ks regulate metabolism, survival, and growth/differentiation in cells including cardiomyocytes (Cantley, 2002;Engelman et al, 2006).…”

Section: Pi3kmentioning

confidence: 99%

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Reichelt

O’Brien

Thomas

et al. 2017

The International Journal of Biochemistry & Cell Biology

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Section: Pi3kmentioning

confidence: 99%

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Reichelt

O’Brien

Thomas

et al. 2017

The International Journal of Biochemistry & Cell Biology

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“…Similarly, overexpression of PTEN inactivates Akt1 [40] and causes a reduction in cell size [41][42][43]. Conversely, expression of a dominant-negative mutant form of PTEN in the heart induces cardiac hypertrophy [44].…”

Section: Heart Failure and Angiotensin IImentioning

confidence: 99%

Angiotensin II as candidate of cardiac cachexia

Delafontaine

Akao

2006

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review-Congestive heart failure is increasing in prevalence and represents a major public health problem. The syndrome of advanced heart failure often includes muscle wasting, commonly termed cardiac cachexia, which is a predictor of poor outcome. Mechanisms of cardiac cachexia are poorly understood, but there is recent evidence that increased angiotensin II, interacting with the insulin-like growth factor-1 system, plays an important role.Recent findings-In animals, angiotensin II produces weight loss through a pressorindependent mechanism, accompanied by decreased levels of circulating and skeletal muscle insulin-like growth factor-1 and increased mRNA levels of the ubiquitin ligases atrogin-1 and Muscle RING finger-1 in skeletal muscle. Reduced insulin-like growth factor-1 action in muscle leads to increased proteolysis, through the ubiquitin-proteasome pathway, and increased apoptosis. These changes are blocked by muscle-specific expression of insulin-like growth factor-1, likely to be via the Akt/mTOR/p70S6K signaling pathway.Summary-The link between insulin-like growth factor-1, the ubiquitin-proteasome pathway, and angiotensin II effects has widespread clinical implications for the understanding of mechanisms of catabolic conditions. Therapeutic interventions targeting cross-talk mechanisms between angiotensin II and insulin-like growth factor-1 effects could provide new approaches for the treatment of muscle wasting.

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“…CTMP, as a pivotal target of AKT, also plays an important role in pathological cardiac hypertrophy. Although PTEN33 and CTMP are negative regulators of AKT, their roles are unexpectedly different in pathological cardiac hypertrophy induced by AB, which is associated with basal myocardial contractility33, 34 and molecular mechanisms in pathological cardiac hypertrophy. Intriguingly, PTEN33 and CTMP exert the same effect in pathological cardiac hypertrophy induced by AngII.…”

Section: Discussionmentioning

confidence: 98%

Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway

Liu

Yang

Zhu

et al. 2018

JAHA

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BackgroundCarboxyl‐terminal modulator protein (CTMP) has been implicated in cancer, brain injury, and obesity. However, the role of CTMP in pathological cardiac hypertrophy has not been identified.Methods and ResultsIn this study, decreased expression of CTMP was observed in both human failing hearts and murine hypertrophied hearts. To further explore the potential involvement of CTMP in pathological cardiac hypertrophy, cardiac‐specific CTMP knockout and overexpression mice were generated. In vivo experiments revealed that CTMP deficiency exacerbated the cardiac hypertrophy, fibrosis, and function induced by pressure overload, whereas CTMP overexpression alleviated the response to hypertrophic stimuli. Consistent with the in vivo results, adenovirus‐mediated gain‐of‐function or loss‐of‐function experiments showed that CTMP also exerted a protective effect against hypertrophic responses to angiotensin II in vitro. Mechanistically, CTMP ameliorated pathological cardiac hypertrophy through the blockade of the protein kinase B signaling pathway. Moreover, inhibition of protein kinase B activation with LY294002 rescued the deteriorated effect in aortic banding–treated cardiac‐specific CTMP knockout mice.ConclusionsTaken together, these findings imply, for the first time, that increasing the cardiac expression of CTMP may be a novel therapeutic strategy for pathological cardiac hypertrophy.

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Regulation of Myocardial Contractility and Cell Size by Distinct PI3K-PTEN Signaling Pathways

Cited by 545 publications

References 45 publications

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

Angiotensin II as candidate of cardiac cachexia

Carboxyl‐Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway

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