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Title: Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

Abstract

Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

Authors:
 [1];  [2]; ; ;  [3];  [4]; ;  [1];  [1];  [2];  [1];  [2];  [2];  [1];  [2];  [2]
  1. Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States)
  2. (United States)
  3. Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)
  4. Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States)
Publication Date:
OSTI Identifier:
22207522
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 414; Journal Issue: 1; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AGING; ANDROGENS; ATROPHY; MESSENGER-RNA; MUSCLES; NOTCHES; PROTEINS; RATS

Citation Formats

Liu, Xin-Hua, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Yao, Shen, Qiao, Rui-Fang, Levine, Alice C., Kirschenbaum, Alexander, Pan, Jiangping, Wu, Yong, Qin, Weiping, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Bauman, William A., Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029, Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, and Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression. United States: N. p., 2011. Web. doi:10.1016/J.BBRC.2011.09.048.
Liu, Xin-Hua, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Yao, Shen, Qiao, Rui-Fang, Levine, Alice C., Kirschenbaum, Alexander, Pan, Jiangping, Wu, Yong, Qin, Weiping, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Bauman, William A., Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029, Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, & Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression. United States. doi:10.1016/J.BBRC.2011.09.048.
Liu, Xin-Hua, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Yao, Shen, Qiao, Rui-Fang, Levine, Alice C., Kirschenbaum, Alexander, Pan, Jiangping, Wu, Yong, Qin, Weiping, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Bauman, William A., Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029, Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, and Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029. Fri . "Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression". United States. doi:10.1016/J.BBRC.2011.09.048.
@article{osti_22207522,
title = {Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression},
author = {Liu, Xin-Hua and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 and Yao, Shen and Qiao, Rui-Fang and Levine, Alice C. and Kirschenbaum, Alexander and Pan, Jiangping and Wu, Yong and Qin, Weiping and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 and Bauman, William A. and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 and Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 and Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu and Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 and Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029},
abstractNote = {Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.},
doi = {10.1016/J.BBRC.2011.09.048},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 414,
place = {United States},
year = {Fri Oct 14 00:00:00 EDT 2011},
month = {Fri Oct 14 00:00:00 EDT 2011}
}