Gouspillou 2015 Sci Rep

From Bioblast
Publications in the MiPMap
Gouspillou G, Scheede-Bergdahl C, Spendiff S, Vuda M, Meehan B, Mlynarski H, Archer-Lahlou E, Sgarioto N, Purves-Smith FM, Konokhova Y, Rak J, Chevalier S, Taivassalo T, Hepple RT, Jagoe RT (2015) Anthracycline-containing chemotherapy causes long-term impairment of mitochondrial respiration and increased reactive oxygen species release in skeletal muscle. Sci Rep 5:8717.

Β» PMID: 25732599 Open Access

Gouspillou Gilles, Scheede-Bergdahl Celena, Spendiff Sally, Vuda Madhusudanarao, Meehan Brian, Mlynarski Heather, Archer-Lahlou Eldoie, Sgarioto Nicolas, Purves-Smith Fennigje M, Konokhova Yana, Rak Janusz, Chevalier Stephanie, Taivassalo Tanja, Hepple Russell T, Jagoe R Thomas (2015) Sci Rep

Abstract: Anticancer treatments for childhood acute lymphoblastic leukaemia (ALL) are highly effective but are now implicated in causing impaired muscle function in long-term survivors. However, no comprehensive assessment of skeletal muscle mitochondrial functions in long-term survivors has been performed and the presence of persistent chemotherapy-induced skeletal muscle mitochondrial dysfunction remains a strong possibility. Non-tumour-bearing mice were treated with two drugs that have been used frequently in ALL treatment (doxorubicin and dexamethasone) for up to 4 cycles at 3-week intervals and euthanized 3 months after the 4th cycle. Treated animals had impaired growth and lower muscle mass as well as reduced mitochondrial respiration and increased reactive oxygen species production per unit oxygen consumption. Mitochondrial DNA content and protein levels of key mitochondrial membrane proteins and markers of mitochondrial biogenesis were unchanged, but protein levels of Parkin were reduced. This suggests a novel pattern of chemotherapy-induced mitochondrial dysfunction in skeletal muscle that persists because of an acquired defect in mitophagy signaling. The results could explain the observed functional impairments in adult survivors of childhood ALL and may also be relevant to long-term survivors of other cancers treated with similar regimes.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: CA Montreal Gouspillou G, CA Montreal Hepple RT, CH Bern Djafarzadeh S

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Cancer 

Organism: Mouse 

HRR: Oxygraph-2k 


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