Premium
Hindlimb Unloading Induces a Biphasic Temporal Response of Bcl‐2 Apoptotic Signaling in the Rat Soleus Muscle
Author(s) -
Propst Gregory Keith,
Kwak HyoBum,
Kim JongHee,
Dalton Ryan Lee,
Lawler John M
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1238.20
Subject(s) - soleus muscle , apoptosis , denervation , hindlimb , atrophy , medicine , endocrinology , muscle atrophy , chemistry , skeletal muscle , caspase 3 , oxidative stress , signal transduction , biology , microbiology and biotechnology , biochemistry , programmed cell death
It is now a widely accepted belief that oxidative stress and apoptosis contribute to muscle atrophy in a number of pathologies including severe disuse (e.g., hindlimb unloading (HU), mechanical ventilation), denervation, and congestive heart failure. Severe disuse induces skeletal muscle atrophy through activation of caspase‐3, apoptosis, calpains, and nuclear factor kappa‐B (NF‐κB) during 2–14 days of unloading. Recent data indicates apoptosis in muscle continues 28 days following denervation. We hypothesize that consistent with denervation data and the “constant proportion model,” pro‐apoptotic signaling would remain elevated after long‐term HU (28 days) compared with short‐term HU (2 days). Fischer 344 rats were divided into 3 groups: Control (CON), 2 days of HU (HU2), and 28 days of HU (HU28), after which soleus muscles were extracted. Bax (+117%) and caspase‐3 cleavage (+324%) were increased in the HU2 soleus, while Bcl‐2 levels trended lower (−18%). Contrary to our hypothesis, HU28 decreased Bax levels (−30%), while Bcl‐2 levels were elevated (+95%), and caspase‐3 cleavage trended lower (−15%) than CON. NF‐κB activation was higher than CON at 28 HU. The data indicates that apoptotic signaling during HU is biphasic, rapidly rising early and attenuating pro‐apoptotic signaling during prolonged HU. Our findings suggest a potential role for NF‐κB, and a more dynamic view of the constant domain model.