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The Analysis of Protein Expression Which Involved in Calcium Handling in Diabetic Heart and Effect of PKA Inhibitor on Abnormal Ca2+ Metabolism in Cardiomyocytes

Author: ZhengZuoZuo
Tutor: ZengQingHua
School: Northeast Normal University
Course: Physiology
Keywords: STZ-induced diabetes mellitus Ca2+ overload L-type calcium current SERCA2a NCX Cav1.2 PKA inhibitor
CLC: R587.2
Type: Master's thesis
Year: 2008
Downloads: 84
Quote: 0
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Abstract


Diabetic cardiomyopathy has been suggested to result partly from abnormal intracellular Ca2+ homeostasis in diabetic myocardium, which is regulated by Ca2+ handling proteins such as sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA), sarcolemmal Na+/Ca2+ exchanger (NCX) and L-type Ca2+ channel protein etc.. However, the responsible molecular mechanisms are unclear. The present study aimed to investigate expression of mRNAs and proteins related to intracellular Ca2+ metabolism in the STZ induced diabetic rat heart. The results show that expression of SERCA2a was significantly less in cardiac muscle 4 weeks after STZ injection than that in the age matched controls. In contrast, expression of NCX mRNA increased in diabetic rat heart compared to controls,mRNA coding voltage-dependent L-type Ca2+ channel (Cav1.2) was not changed markly. The results of immunobloting which show the level of Ca2+ handling proteins were consistent with RT-PCRs, however the amplitude of L-type Ca2+ current (ICa) was significantly reduced in diabetes in the range of test potentials between -50 and +50 mV. Moreover, the basal level of Ca2+ concentration of diabetic myocardial cell was increased 52.7%. Incubating cardiomyocytes with selective PKA inhibitor H-89 significantly restored the altered parameters of Ca2+ concentration in diabetic rats from 267.669±3.895nM to 195.883±1.02nM and perifusion with H-89 also make ICa lower (nearly 48.3% decrease). Thus it is conclude that defects in cardiac muscle partly caused by alteration of expression of proteins that regulate [Ca2+]i and by structural and/or functional changes in L-type Ca2+ channel in streptozotocin(STZ) induced diabetic rats and PKA participate in the abnormal Ca2+ metabolism.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Islet disease > Diabetic coma and other complications
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