title: Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression.
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.affiliation: Center of Excellence for Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468, USA.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Shen
authors.initials: S
authors.lastname: Yao
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Qiao
authors.forename: Alice C
authors.initials: AC
authors.lastname: Levine
authors.forename: Alexander
authors.initials: A
authors.lastname: Kirschenbaum
authors.forename: Jiangping
authors.initials: J
authors.lastname: Pan
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Weiping
authors.initials: W
authors.lastname: Qin
authors.forename: William A
authors.initials: WA
authors.lastname: Bauman
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cardozo
mesh_terms: D045930:Anabolic Agents / Q000008:administration & dosage*; D000728:Androgens / Q000008:administration & dosage*; D000818:Animals; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism; D009133:Muscular Atrophy / Q000378:metabolism / Q000517:prevention & control*; D009277:Nandrolone / Q000008:administration & dosage*; D051381:Rats; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D045930:Anabolic Agents; D000728:Androgens; D047908:Intracellular Signaling Peptides and Proteins; D051880:Receptors, Notch; C559994:numb protein, rat; D009277:Nandrolone