Inhibition of PHLPP1 ameliorates cardiac dysfunction via activation of the PI3K/Akt/mTOR signalling pathway in diabetic cardiomyopathy.

Journal of Cellular and Molecular Medicine
Mingjun ZhangFengshuang An

Abstract

Pleckstrin homology (PH) domain leucine-rich repeat protein phosphatase 1 (PHLPP1) is a kind of serine/threonine phosphatase, whose dysregulation is accompanied with numerous human diseases. However, its role in diabetic cardiomyopathy remains unclear. We explored the underlying function and mechanism of PHLPP1 in diabetic cardiomyopathy (DCM). In vivo, Type 1 diabetic rats were induced by intraperitoneal injection of 60 mg/kg streptozotocin (STZ). Lentivirus-mediated short hairpin RNA (shRNA) was used to knock down the expression of PHLPP1. In vitro, primary neonatal rat cardiomyocytes and H9C2 cells were incubated in 5.5 mmol/L glucose (normal glucose, NG) or 33.3 mmol/L glucose (high glucose, HG). PHLPP1 expression was inhibited by PHLPP1-siRNA to probe into the function of PHLPP1 in high glucose-induced apoptosis in H9c2 cells. Diabetic rats showed up-regulated PHLPP1 expression, left ventricular dysfunction, increased myocardial apoptosis and fibrosis. PHLPP1 inhibition alleviated cardiac dysfunction. Additionally, PHLPP1 inhibition significantly reduced HG-induced apoptosis and restored PI3K/AKT/mTOR pathway activity in H9c2 cells. Furthermore, pretreatment with LY294002, an inhibitor of PI3K/Akt/mTOR pathway, abolished t...Continue Reading

References

Nov 10, 2001·Trends in Biochemical Sciences·D P Brazil, B A Hemmings
Feb 26, 2004·Journal of Vascular Nursing : Official Publication of the Society for Peripheral Vascular Nursing·Phyllis A Gordon
Aug 6, 2004·Endocrine Reviews·Zhi You FangThomas H Marwick
Dec 14, 2005·Pharmacology & Therapeutics·Hana FarhangkhoeeSubrata Chakrabarti
Feb 21, 2006·Journal of the American College of Cardiology·Juan Asbun, Francisco J Villarreal
Oct 19, 2006·Journal of the American College of Cardiology·Maurizio Galderisi
Jun 27, 2007·Circulation·Sihem Boudina, E Dale Abel
May 31, 2008·Trends in Endocrinology and Metabolism : TEM·John Brognard, Alexandra C Newton
Jul 15, 2009·Journal of Molecular and Cellular Cardiology·Lisandro Maya, Francisco J Villarreal
Oct 1, 2009·The Biochemical Journal·Jad WaltersA Clay Clark
Oct 30, 2010·Circulation Research·Ferdinando Giacco, Michael Brownlee
Dec 7, 2011·The Journal of Biological Chemistry·Noel A Warfel, Alexandra C Newton
Feb 22, 2012·The FEBS Journal·Audrey K O'NeillAlexandra C Newton
May 29, 2012·Archives of Cardiovascular Diseases·Laura Ernande, Geneviève Derumeaux
May 4, 2013·European Heart Journal·Francesco PaneniFrancesco Cosentino
Oct 29, 2013·Cell Death and Differentiation·N VolkmannD Hanein
Dec 18, 2013·Pharmacology & Therapeutics·Jiri Polivka, Filip Janku
Jan 28, 2014·Pharmacology & Therapeutics·Karina HuynhRebecca H Ritchie
Nov 21, 2014·Cardiovascular Research·Courtney MocNicole H Purcell
Jun 30, 2015·Molecular Cell·Esperanza AriasAna María Cuervo
Dec 26, 2015·Journal of Molecular and Cellular Cardiology·Ilaria Russo, Nikolaos G Frangogiannis
Mar 14, 2016·International Immunopharmacology·Da-Cai TengYang Shi
Jul 9, 2016·Nature Reviews. Endocrinology·Paul ZimmetPeter H Bennett
Dec 6, 2016·Pharmacology & Therapeutics·Alyssa Faria, Shanta J Persaud
Dec 15, 2017·BioMed Research International·Dou HuangCharbel Abi Khalil
Jan 20, 2018·Journal of the American College of Cardiology·Thomas H MarwickDavid Kaye
Feb 17, 2018·Circulation Research·Guanghong JiaJames R Sowers
Dec 21, 2018·International Journal of Molecular Sciences·Angelo MaffeiDaniela Carnevale

❮ Previous
Next ❯

Citations

Jan 13, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Samantha R WeaverJennifer J Westendorf
Jun 16, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bin ZhangXiaobo Sun
Aug 5, 2021·Cell Reports·Blaz LupseAmin Ardestani

❮ Previous
Next ❯

Methods Mentioned

BETA
fluorescence microscopy
Protein Assay
electrophoresis
PCR

Software Mentioned

VisualSonic
ImageJ
Prism
SPSS

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis