EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES

Bibliographic Details
Main Author:	SONG, QIUJING
Language:	English
Published:	University of Cincinnati / OhioLINK 2004
Subjects:	phospholamban cardiac function slow-twitch skeletal muscle
Online Access:	http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100807947

id	ndltd-OhioLink-oai-etd.ohiolink.edu-ucin1100807947
record_format	oai_dc
spelling	ndltd-OhioLink-oai-etd.ohiolink.edu-ucin11008079472021-08-03T06:10:00Z EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES SONG, QIUJING phospholamban cardiac function slow-twitch skeletal muscle The major function of the sarcoplasmic reticulum (SR) in Ca <sup>2+</sup> homeostasis and contractility in cardiac and slow-twitch skeletal muscles is tightly regulated by the SR Ca <sup>2+</sup> ATPase (SERCA2a) and its crucial inhibitor phospholamban (PLN). The present dissertation investigated: 1) the role of PLN in cardiac muscle with specific emphasis on evaluation of the efficacy of PLN inhibition on contractile dysfunction and remodeling; and 2) the physiological significance of PLN in slow-twitch skeletal muscle. 1) In cardiac muscle, mounting evidence has shown depressed SR Ca <sup>2+</sup> cycling is a hallmark feature of failing heart. Normalization of Ca <sup>2+</sup> cycling by ablation or inhibition of the SERCA2a inhibitor PLN has prevented cardiac failure in experimental dilated cardiomyopathy. However, the potential benefits of restoring SR function on primary cardiac hypertrophy, a common antecedent of heart failure, remain unknown. We therefore tested the efficacy of PLN ablation in preventing the ventricular failure of Gαq overexpression induced cardiac hypertrophy. PLN ablation normalized the characteristically prolonged cardiomyocyte Ca <sup>2+</sup> transients and enhanced unloaded fractional shortening with no change in SR Ca <sup>2+</sup> pump abundance in the Gαq overexpressor. Despite “rescue” of cardiomyocyte mechanical function and Ca <sup>2+</sup> signaling, there was no parallel improvement in <i>in vivo</i> cardiac function. Furthermore, PLN ablation was unable to alleviate Gαq-induced hypertrophic remodeling. These findings indicated restoration of SR Ca <sup>2+</sup> cycling by PLN ablation was not sufficient to prevent the ventricular failure of the Gαq-induced cardiac hypertrophy. 2) In transgenic mice with PLN specific overexpression in slow-twitch skeletal muscle, the PLN protein levels and the PLN/SERCA2a ratio in transgenic soleus were comparable to those in cardiac muscle. The isometric-twitch contractile performance was significantly depressed in PLN overexpressing soleus, but isopreterenol stimulation relieved the inhibitory effects of PLN. Interestingly, PLN-overexpression was associated with considerable reduction in soleus mass and increased slow-fiber percentage. Therefore, increased PLN expression in slow-twitch skeletal muscle leads to impaired contractile function and muscle remodeling. In summary, the present dissertation revealed the importance of PLN protein level regulation in maintaining normal function and morphology of both cardiac and slow-twitch skeletal muscles in mice. 2004 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100807947 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100807947 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection	NDLTD
language	English
sources	NDLTD
topic	phospholamban cardiac function slow-twitch skeletal muscle
spellingShingle	phospholamban cardiac function slow-twitch skeletal muscle SONG, QIUJING EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES
author	SONG, QIUJING
author_facet	SONG, QIUJING
author_sort	SONG, QIUJING
title	EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES
title_short	EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES
title_full	EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES
title_fullStr	EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES
title_full_unstemmed	EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES
title_sort	effects of genetic manipulation of phospholamban protein levels on contractile function and remodeling in murine cardiac and slow-twitch skeletal muscles
publisher	University of Cincinnati / OhioLINK
publishDate	2004
url	http://rave.ohiolink.edu/etdc/view?acc_num=ucin1100807947
work_keys_str_mv	AT songqiujing effectsofgeneticmanipulationofphospholambanproteinlevelsoncontractilefunctionandremodelinginmurinecardiacandslowtwitchskeletalmuscles
_version_	1719432026750189568

EFFECTS OF GENETIC MANIPULATION OF PHOSPHOLAMBAN PROTEIN LEVELS ON CONTRACTILE FUNCTION AND REMODELING IN MURINE CARDIAC AND SLOW-TWITCH SKELETAL MUSCLES

Similar Items