Glycogen synthase kinase 3beta together with 14-3-3 protein regulates diabetic cardiomyopathy: effect of losartan and tempol

FEBS Letters
Narasimman GurusamyYoshifusa Aizawa

Abstract

Glycogen synthase kinase (GSK) 3beta is a multifunctional protein that positively regulates myocardial apoptosis and negatively regulates hypertrophy. However, the role of GSK3beta in the diabetic myocardium is largely unknown. We found that GSK3beta became more active (less phosphorylated at serine 9) via decreased Akt phosphorylation, in parallel to c-Jun NH2 terminal kinase activation, which correlated with increased activated caspase 3 and myocardial apoptosis 3 days after streptozotocin (STZ) injection in mice. However, 28 days after STZ injection, GSK3beta became inactive, which correlated with the enhanced protein kinase C beta2 and p38 mitogen activated protein kinase expression, nuclear translocation of nuclear factor of activated T cells c3, cardiac hypertrophy and fibrosis. All of the above parameters were exacerbated in dominant-negative 14-3-3 transgenic mice. Our results suggest that GSK3beta together with 14-3-3 protein plays essential roles in the signaling of diabetic cardiomyopathy, and treatment with either losartan or tempol prevents these changes.

References

Jun 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·A B RobertsJ H Kehrl
Apr 26, 2000·Laboratory Investigation; a Journal of Technical Methods and Pathology·F FiordalisoJ Kajstura
Aug 6, 2000·British Journal of Pharmacology·K WatanabeY Aizawa
Jan 11, 2000·Circulation Research·A FrustaciP Anversa
Sep 5, 2001·The Journal of Biological Chemistry·L M BallouR Z Lin
Sep 21, 2001·The Biochemical Journal·S Frame, P Cohen
Nov 21, 2001·The Journal of Clinical Investigation·M TakemotoJ K Liao
Jan 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Christopher L AntosEric N Olson
Jan 31, 2002·Drugs·Steven J Lavine, Steven D Gellman
Jun 1, 2002·Circulation Research·Stefan E Hardt, Junichi Sadoshima
Jul 26, 2002·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Daniela GrimmEckhard P Kromer
Jul 23, 2003·Journal of the American Society of Nephrology : JASN·Toyoshi InoguchiHajime Nawata
Jul 9, 2004·Biochemical and Biophysical Research Communications·Narasimman GurusamyYoshifusa Aizawa
Jul 28, 2004·Cardiovascular Research·Stefan E Hardt, Junichi Sadoshima
Aug 6, 2004·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Yağiz UresinAli Osman Gürol

❮ Previous
Next ❯

Citations

Jul 6, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Siddhartha S GhoshRakesh C Kukreja
Jul 12, 2011·Physiological Reviews·Mark A SussmanMichael McGregor
Mar 30, 2007·Congestive Heart Failure·George W Booz
Mar 18, 2008·Biochemical Pharmacology·Rajarajan A ThandavarayanYoshifusa Aizawa
Aug 27, 2009·Acta Physiologica Hungarica·Kenichi WatanabeY Aizawa
Oct 30, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Sayantani ChowdhuryParames C Sil
Dec 20, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Rajarajan A ThandavarayanKenichi Watanabe
Mar 30, 2007·Journal of Pharmacological and Toxicological Methods·Pitchai BalakumarManjeet Singh
Oct 17, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Ken-ichi WatanabeYoshifusa Aizawa
Nov 26, 2014·Journal of Diabetes Investigation·Quan LiuLu Cai
Oct 13, 2009·American Journal of Physiology. Heart and Circulatory Physiology·S Ares-CarrascoO Lorenzo
Jul 21, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Rajarajan A ThandavarayanYoshifusa Aizawa

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

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

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.

Cardiomegaly

Cardiomegaly, known as an enlarged heart, is a multifactorial disease with different pathophysiological mechanisms. Hypertension, pregnancy, exercise-induced and idiopathic causes are some mechanisms of cardiomegaly. Discover the latest research of cardiomegaly here.