title: Conessine Interferes with Oxidative Stress-Induced C2C12 Myoblast Cell Death through Inhibition of Autophagic Flux.
abstract: Conessine, a steroidal alkaloid isolated from Holarrhena floribunda, has anti-malarial activity and interacts with the histamine H3 receptor. However, the cellular effects of conessine are poorly understood. Accordingly, we evaluated the involvement of conessine in the regulation of autophagy. We searched natural compounds that modulate autophagy, and conessine was identified as an inhibitor of autophagic flux. Conessine treatment induced the formation of autophagosomes, and p62, an autophagic adapter, accumulated in the autophagosomes. Reactive oxygen species such as hydrogen peroxide (H2O2) result in muscle cell death by inducing excessive autophagic flux. Treatment with conessine inhibited H2O2-induced autophagic flux in C2C12 myoblast cells and also interfered with cell death. Our results indicate that conessine has the potential effect to inhibit muscle cell death by interfering with autophagic flux.
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.
authors.forename: Hyunju
authors.initials: H
authors.lastname: Kim
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.
authors.forename: Kang Il
authors.initials: KI
authors.lastname: Lee
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.
authors.forename: Minsu
authors.initials: M
authors.lastname: Jang
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.
authors.forename: Sim
authors.initials: S
authors.lastname: Namkoong
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.
authors.forename: Rackhyun
authors.initials: R
authors.lastname: Park
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.
authors.forename: Hyunwoo
authors.initials: H
authors.lastname: Ju
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.
authors.forename: Inho
authors.initials: I
authors.lastname: Choi
authors.affiliation: Korea Bioactive Natural Material Bank, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
authors.forename: Won Keun
authors.initials: WK
authors.lastname: Oh
authors.affiliation: Division of Biological Science and Technology, Yonsei University, Wonju, 26493, Republic of Korea.
authors.forename: Junsoo
authors.identifier: http://orcid.org/0000-0002-2355-6760
authors.initials: J
authors.lastname: Park
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000071182:Autophagosomes / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D061986:MCF-7 Cells; D051379:Mice; D018613:Microscopy, Confocal; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species
chemical_list: D000470:Alkaloids; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; C007111:conessine