Studies of Mitochondrial and Nonmitochondrial Sources Implicate Nicotinamide Adenine Dinucleotide Phosphate Oxidase(s) in the Increased Skeletal Muscle Superoxide Generation That Occurs During Contractile Activity

• DOI: 10.1089/ars.2012.4623
• Publication Date: 2012-10-11T06:36:31Z
• Authors: Giorgos Konstanti...; Aphrodite Vasilaki; Jesus Palomero; Anna Kayani; Lea Zibrik; Anne McArdle; Malcolm J. Jackson
• Keywords: Sarcolemma

The sources of cytosolic superoxide in skeletal muscle have not been defined. This study examined the subcellular sites that contribute to mature single fibers at rest and during contractile activity.Isolated from mouse flexor digitorum brevis loaded with nitric-oxide-sensitive fluorescent probes, specific pathway inhibitors immunolocalization techniques were used identify contributing superoxide. Treatment electron transport chain complex III inhibitor, antimycin A, but I rotenone, caused increased through release mitochondrial intermembrane space via voltage-dependent anion or Bax channels, inhibition these channels did affect contraction-induced increases Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase decreased following contractions. Protein mRNA expression NADPH subunits was demonstrated fibers. NOX2, NOX4, p22(phox) localized sarcolemma transverse tubules; NOX4 additionally expressed mitochondria. Regulatory p40(phox) p67(phox) proteins found cytoplasm resting fibers, contractions, appeared translocate sarcolemma.Superoxide other reactive oxygen species generated by are important regulators force production adaptations has defined relative contribution within cytosol contractions.Muscle mitochondria do modulate is a major contributor both