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Regulation of neuregulin/ErbB signal...

LeBrasseur, Nathan Kyle.

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Regulation of neuregulin/ErbB signaling in skeletal muscle.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Regulation of neuregulin/ErbB signaling in skeletal muscle./
作者:	LeBrasseur, Nathan Kyle.
面頁冊數:	94 p.
附註:	Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 1981.
Contained By:	Dissertation Abstracts International64-05B.
標題:	Biology, Cell. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3090415

Regulation of neuregulin/ErbB signaling in skeletal muscle.
LeBrasseur, Nathan Kyle.

Regulation of neuregulin/ErbB signaling in skeletal muscle. - 94 p.

Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 1981.

Thesis (Ph.D.)--Boston University, 2003.

The <bolditalic>neuregulins</bolditalic> (NRGs) are a complex family of epidermal growth factor-like molecules that mediate an array of cellular responses including growth, differentiation and survival by activating members of the <bolditalic>ErbB</bolditalic> family of receptor tyrosine kinases. Putative roles of NRG and the ErbB receptors in skeletal muscle biology include myogenesis, acetylcholine receptor expression and glucose transport. Prior to the work detailed here, however, the expression and physiologic regulation of NRG/ErbB signaling in adult skeletal muscle had not been examined. Thus, the hypotheses that multiple NRG isoforms and the ErbB2, ErbB3 and ErbB4 receptors are expressed in adult skeletal muscle, and contractile activity <italic> in vivo</italic> induces NRG/ErbB activation were tested. Rat hind limb muscle contraction was elicited with a single bout of electrical stimulation (RX) or treadmill running (EX). Western blot and immunofluorescence confirmed the expression of multiple NRG isoforms and the ErbB2, ErbB3 and ErbB4 receptors in adult skeletal muscle.{09}Both RX and EX significantly increased phosphorylation of all NRG receptors.{09}Furthermore, contraction induced a shift in the expression profile of NRG, consistent with proteolytic processing of a transmembrane isoform. Thus two distinct modes of exercise activated processing of NRG with concomitant stimulation of ErbB2, ErbB3 and ErbB4 signaling <italic>in vivo </italic>. To further assess the contribution of this system to exercise signaling, the next study characterized the downstream signaling events associated with NRG-mediated activation of the ErbB receptors. Following incubation in the absence or presence of NRG-1β, rat soleus and EDL muscles demonstrated significant phosphorylation of ErbB2-4 receptors and the Erk1/2 and Akt signaling substrates. Furthermore, we examined the role of mechanical stretch in skeletal muscle on the activation of NRG/ErbB signaling <italic>in vitro, in vivo</italic>, and in isolated myotubes. These studies demonstrated that while static stretch failed to stimulate NRG/ErbB signaling in adult tissue <italic>in vitro</italic> and <italic>in vivo</italic>, cyclic stretch activated NRG/ErbB autocrine signaling in C2C12 cells in culture. The findings detailed in this dissertation provide novel insight regarding the physiological regulation of NRG/ErbB signaling in skeletal muscle, and implicate this pathway in the metabolic and proliferative responses of skeletal muscle to exercise.Subjects--Topical Terms:

1017686
Biology, Cell.

Regulation of neuregulin/ErbB signaling in skeletal muscle.
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500 $a Source: Dissertation Abstracts International, Volume: 64-05, Section: B, page: 1981.
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520 $a The <bolditalic>neuregulins</bolditalic> (NRGs) are a complex family of epidermal growth factor-like molecules that mediate an array of cellular responses including growth, differentiation and survival by activating members of the <bolditalic>ErbB</bolditalic> family of receptor tyrosine kinases. Putative roles of NRG and the ErbB receptors in skeletal muscle biology include myogenesis, acetylcholine receptor expression and glucose transport. Prior to the work detailed here, however, the expression and physiologic regulation of NRG/ErbB signaling in adult skeletal muscle had not been examined. Thus, the hypotheses that multiple NRG isoforms and the ErbB2, ErbB3 and ErbB4 receptors are expressed in adult skeletal muscle, and contractile activity <italic> in vivo</italic> induces NRG/ErbB activation were tested. Rat hind limb muscle contraction was elicited with a single bout of electrical stimulation (RX) or treadmill running (EX). Western blot and immunofluorescence confirmed the expression of multiple NRG isoforms and the ErbB2, ErbB3 and ErbB4 receptors in adult skeletal muscle.{09}Both RX and EX significantly increased phosphorylation of all NRG receptors.{09}Furthermore, contraction induced a shift in the expression profile of NRG, consistent with proteolytic processing of a transmembrane isoform. Thus two distinct modes of exercise activated processing of NRG with concomitant stimulation of ErbB2, ErbB3 and ErbB4 signaling <italic>in vivo </italic>. To further assess the contribution of this system to exercise signaling, the next study characterized the downstream signaling events associated with NRG-mediated activation of the ErbB receptors. Following incubation in the absence or presence of NRG-1β, rat soleus and EDL muscles demonstrated significant phosphorylation of ErbB2-4 receptors and the Erk1/2 and Akt signaling substrates. Furthermore, we examined the role of mechanical stretch in skeletal muscle on the activation of NRG/ErbB signaling <italic>in vitro, in vivo</italic>, and in isolated myotubes. These studies demonstrated that while static stretch failed to stimulate NRG/ErbB signaling in adult tissue <italic>in vitro</italic> and <italic>in vivo</italic>, cyclic stretch activated NRG/ErbB autocrine signaling in C2C12 cells in culture. The findings detailed in this dissertation provide novel insight regarding the physiological regulation of NRG/ErbB signaling in skeletal muscle, and implicate this pathway in the metabolic and proliferative responses of skeletal muscle to exercise.
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