MicroRNA-434-3p regulates age-related apoptosis through eIF5A1 in the skeletal muscle.
Increased activation of catabolic pathways, including apoptosis causes sarcopenia. However, the precise molecular mechanism that initiates apoptosis during aging is not well understood. Here, we report that aging alters miRNA expression profile in mouse skeletal muscle as evidenced by miRNA microarray and real-time PCR. We identified miR-434-3p as a highly downregulated miRNA in the skeletal muscle of aging mice. Myocytes transfected with miR-434-3p mimic prevents apoptosis induced by various apoptotic stimuli, and co-transfection of miR-434-3p antagomir abolishes the inhibitory role of miR-434-3p. We found that miR-434-3p inhibits apoptosis by targeting the eukaryotic translation initiation factor 5A1 (eIF5A1). Overexpression of miR-434-3p in myocytes reduces the loss of mitochondrial transmembrane potential, and activation of caspases-3, -8 and -9 by suppressing eIF5A1 in response to various apoptotic stimuli whereas inhibition of miR-434-3p reversed this scenario. Skeletal muscles from aging mice exhibit low levels of miR-434-3p and high levels of eIF5A1, suggesting a possible role for miR-434-3p in the initiation of apoptosis in aging muscle. Overall, our data identified for the first time that miR-434-3p is an anti-apoptotic miRNA that may be therapeutically useful for treating muscle atrophy in various pathophysiological conditions, including sarcopenia.
Division of Pulmonary and Critical Care Section, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Patricia S
PS
Pardo
Division of Exercise Physiology, Department of Human Performance, West Virginia University School of Medicine, Morgantown, West Virginia 26506, USA.
Ameena
A
Hajira
Division of Pulmonary and Critical Care Section, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Aladin M
AM
Boriek
Division of Exercise Physiology, Department of Human Performance, West Virginia University School of Medicine, Morgantown, West Virginia 26506, USA.|Center for Basic and Translational Stroke Research, West Virginia University School of Medicine, Morgantown, West Virginia 26506, USA.
Junaith S
JS
Mohamed
D000375:Aging / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D020169:Caspases / Q000378:metabolism; D005786:Gene Expression Regulation; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D032342:Muscle Cells / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000097574:Eukaryotic Translation Initiation Factor 5A
D020169:Caspases; D035683:MicroRNAs; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A
aging; mitochondria; sarcopenia; skeletal muscle