Pharaoh 2020 Sci Rep

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Publications in the MiPMap
Pharaoh G, Brown JL, Sataranatarajan K, Kneis P, Bian J, Ranjit R, Hadad N, Georgescu C, Rabinovitch P, Ran Q, Wren JD, Freeman W, Kinter M, Richardson A, Van Remmen H (2020) Targeting cPLA2 derived lipid hydroperoxides as a potential intervention for sarcopenia. Sci Rep 10:13968.

» PMID: 32811851

Pharaoh Gavin, Brown Jacob L, Sataranatarajan Kavithalakshmi, Kneis Parker, Bian Jan, Ranjit Rojina, Hadad Niran, Georgescu Constantin, Rabinovitch Peter, Ran Qitao, Wren Jonathan D, Freeman Willard, Kinter Michael, Richardson Arlan, Van Remmen Holly (2020) Sci Rep

Abstract: Defects in neuromuscular innervation contribute significantly to the age-related decline in muscle mass and function (sarcopenia). Our previous studies demonstrated that denervation induces muscle mitochondrial hydroperoxide production (H2O2 and lipid hydroperoxides (LOOHs)). Here we define the relative contribution of mitochondrial electron transport chain (ETC) derived H2O2 versus cytosolic phospholipase A2 (cPLA2) derived LOOHs in neurogenic muscle atrophy. We show that denervation increases muscle cPLA2 protein content, activity, and metabolites downstream of cPLA2 including LOOHs. Increased scavenging of mitochondrial H2O2 does not protect against denervation atrophy, suggesting ETC generated H2O2 is not a critical player. In contrast, inhibition of cPLA2 in vivo mitigates LOOH production and muscle atrophy and maintains individual muscle fiber size while decreasing oxidative damage. Overall, we show that loss of innervation in several muscle atrophy models including aging induces generation of LOOHs produced by arachidonic acid metabolism in the cPLA2 pathway contributing to loss of muscle mass.

Bioblast editor: Plangger M O2k-Network Lab: US OK Oklahoma City Van Remmen H


Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Aging;senescence  Stress:Oxidative stress;RONS  Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 



HRR: Oxygraph-2k, O2k-Fluorometer 

2020-08, AmR