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Celecoxib Inhibits Proliferation, Mitochondrial Respiratory Rate, and Membrane Potential in Myoblasts
Author(s) -
Kolb Alexander,
Reynoso Marinaliz,
Geddis Alyssa,
Matheny Ronald
Publication year - 2019
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.2019.33.1_supplement.lb259
Subject(s) - celecoxib , viability assay , myocyte , pharmacology , chemistry , cell growth , fasudil , apoptosis , medicine , phosphorylation , biochemistry , rho associated protein kinase
Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly prescribed for their analgesic and anti‐inflammatory properties, and their use is widespread in the general, athletic, and military populations. It is relatively well‐documented that long‐term consumption of NSAIDs is associated with increased risk of heart attack, stroke, gastrointestinal bleeding, and kidney disease; however, much less is known regarding the positive or negative effects of NSAIDs in skeletal muscle. Given this, we performed a series of experiments to determine the degree and mechanisms through which the NSAID celecoxib perturbs cultured skeletal muscle cell proliferation, intracellular signaling, and mitochondrial function. Myoblasts were incubated with celecoxib or NS‐398 (a selective COX2 inhibitor) for 48‐h. Cell viability was tested using 3‐(4,5‐Dimethylthiazol‐2‐Yl)‐2,5‐Diphenyltetrazolium Bromide (MTT) assay, anabolic signaling pathways were evaluated by Western blot, mitochondrial metabolism was determined via cytochrome c oxidase activity assay, and mitochondrial membrane potential was determined by membrane‐sensitive JC‐1 dye. First, cells were treated with celecoxib at concentrations ranging from 200 μM to 0.1 μM. Cell viability was significantly depressed (100% to 19%; P<0.01) by celecoxib in a dose‐dependent fashion at concentrations from 200 μM to 3.125 μM. Myoblasts treated with NS‐398 showed no decrease in viability. Phosphorylation of ribosomal protein S6 (S240/244) was decreased by 77% in myoblasts treated with 50 μM celecoxib (P<0.05), whereas treatment with NS‐398 had no effect on S6 phosphorylation. Celecoxib inhibited the mitochondrial respiratory rate of the following Kreb's cycle intermediates (percent reduction in parenthesis): cis‐aconitic acid (25%; P<0.01), alpha‐keto‐glutaric acid (50%; P<0.05), succinic acid (45%; P<0.05), and L‐malic acid (37%; P<0.05). Fifty and 25 μM celecoxib reduced mitochondrial membrane potential by 40% and 25%, respectively (P<0.001 for both) Together, these data demonstrate that decreased myoblast viability following celecoxib treatment was associated with reductions in proliferative signaling, mitochondrial enzyme activity, and membrane potential. The mechanism(s) and degree to which celexoxib‐induced perturbations of mitochondrial enzyme activity influence myoblast viability remain to be determined. The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government. This abstract has been approved for public release with unlimited distribution. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .