title: Novel mitochondria-targeted antioxidant peptide ameliorates burn-induced apoptosis and endoplasmic reticulum stress in the skeletal muscle of mice.
abstract: This study tested the hypothesis that a novel mitochondria-targeted SS-31 peptide attenuates the burn injury-induced apoptosis and endoplasmic reticulum stress and improves insulin sensitivity in the skeletal muscle. Following 30% total body surface area burn or sham burn, mice were injected daily with SS-31 peptide (5 mg/kg body weight), and the rectus abdominis muscles collected on postburn days 1, 3, and 7. The tissues were subjected to various biochemical and immunohistochemical analyses. Treatment with SS-31 peptide prevented burn-induced increases in the caspase 3 activity (P < 0.05) and apoptosis (P < 0.01) on postburn day 7. The SS-31 peptide treatment also prevented the increase in the expression levels of phosphatase and tensin homolog on postburn days 3 and 7. Burn injury-induced increases in the levels of two endoplasmic reticulum stress markers, binding immunoglobulin protein and protein disulfide isomerase, were significantly decreased by the SS-31 peptide treatments on postburn day 7 and on day 3 for binding immunoglobulin protein as well (P < 0.05). The effects of SS-31 appear to be, in part, due to its ability to reduce oxidative stress in burned mice, evidenced by reduced expression of oxidized proteins that were clearly evident on postburn day 7. Our results demonstrate a possible therapeutic potential of SS-31 peptide to ameliorate the adverse effects of burn injury in skeletal muscle.
authors.affiliation: Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors.forename: Hyung-yul
authors.initials: HY
authors.lastname: Lee
authors.forename: Masao
authors.initials: M
authors.lastname: Kaneki
authors.forename: Jonathan
authors.initials: J
authors.lastname: Andreas
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Tompkins
authors.forename: J A Jeevendra
authors.initials: JA
authors.lastname: Martyn
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002056:Burns / Q000150:complications* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009842:Oligopeptides / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D009842:Oligopeptides; D017382:Reactive Oxygen Species; C506540:arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide