title: Evaluation of two novel antioxidants with differential effects on curcumin-induced apoptosis in C2 skeletal myoblasts; involvement of JNKs.
abstract: Excessive levels of reactive oxygen species (ROS) result in numerous pathologies including muscle disorders. In essence, skeletal muscle performance of daily activities can be severely affected by the redox imbalances occurring after muscular injuries, surgery, atrophy due to immobilization, dystrophy or eccentric muscle contraction. Therefore, research on the potential beneficial impact of antioxidants is of outmost importance. In this context, aiming at further exploring the mechanisms of action of our newly synthesized antioxidant compounds (AK1 and AK2) in a skeletal muscle experimental setting, we initially investigated their scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) and subsequently assessed their effect on the viability of C2 skeletal myoblasts in the presence of two pro-oxidants: H2O2 and curcumin (MTT assay). Interestingly, while both compounds reversed the detrimental effect of H2O2, only AK2 was cytoprotective in curcumin-treated C2 cells. We next confirmed the immediate activation of extracellular signal-regulated kinases (ERKs) and the more delayed activation profile of c-Jun NH2-terminal kinases (JNKs) in C2 skeletal myoblasts exposed to curcumin, by Western blotting. In correlation with the aforementioned results, only AK2 blocked the curcumin-induced activation of JNKs pathway. Furthermore, JNKs were revealed to mediate curcumin-induced apoptosis in C2 cells and only AK2 to effectively suppress it (by detecting its effect on poly(ADP-ribose) polymerase fragmentation). Overall, we have shown that two similar in structure novel antioxidants confer differential effects on C2 skeletal myoblasts viability under oxidative stress conditions. This result may be attributed to these antioxidants respective diverse mode of interaction with the signaling effectors involved in the observed responses. Future studies should further evaluate the mechanism of action of these compounds in order to support their potential application in therapeutic protocols against ROS-related muscle disorders.
authors.affiliation: Department of Animal and Human Physiology, School of Biology, University of Athens, University Campus, Athens 157 84, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Peleli
authors.affiliation: Department of Animal and Human Physiology, School of Biology, University of Athens, University Campus, Athens 157 84, Greece.
authors.forename: Ioanna-Katerina
authors.initials: IK
authors.lastname: Aggeli
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Athens, Athens 157 71, Greece.
authors.forename: Alexios N
authors.initials: AN
authors.lastname: Matralis
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, University of Athens, Athens 157 71, Greece.
authors.forename: Angeliki P
authors.initials: AP
authors.lastname: Kourounakis
authors.affiliation: Department of Animal and Human Physiology, School of Biology, University of Athens, University Campus, Athens 157 84, Greece.
authors.forename: Isidoros
authors.initials: I
authors.lastname: Beis
authors.affiliation: Department of Animal and Human Physiology, School of Biology, University of Athens, University Campus, Athens 157 84, Greece. Electronic address: cgaitan@biol.uoa.gr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Gaitanaki
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D048031:JNK Mitogen-Activated Protein Kinases; D003474:Curcumin
keywords: Antioxidant; Apoptosis; C2 skeletal myoblasts; Curcumin; ERKs; JNKs; ROS