Botulinum toxin type A induces protective autophagy in human dermal microvascular endothelial cells exposed to an in vitro model of ischemia/reperfusion injury.

Content Provider	Europe PMC
Author	Shi, Yanyu Lin, Huang Cao, Jiankun Cui, Chao
Copyright Year	2018
Abstract	Botulinum toxin type A (BTXA) has been reported to increase the survival of ischemic skin flaps; however, the exact mechanism underlying this effect remains unclear and needs to be further established. The present study aimed to elucidate whether autophagy caused by BTXA functions as a protection mechanism and to identify the mechanisms of its regulation by BTXA in human dermal microvascular endothelial cells (HDMECs) subjected to hypoxia/reoxygenation (H/R)-induced injury. HDMECs were harvested from the upper eyelid tissues of female blepharoplasty patients. HDMECs were exposed to BTXA treatment for 12 h and then subjected to hypoxia for 8 h, followed by reoxygenation for 24 h. Chloroquine diphosphate salt (CQ) was used as an autophagy inhibitor. H/R led to extreme injury to the HDMECs as indicated by the rise in the apoptosis rate, which was significantly attenuated by BTXA pretreatment. The outcomes demonstrated that H/R caused autophagy, as evidenced by a higher type II/type I ratio of light chain 3 (LC3), increased expression of Beclin-1 and increased autophagosome formation. BTXA enhanced autophagy and attenuated apoptosis in a dose-dependent manner, whereas CQ attenuated the BTXA antiapoptotic effects and inhibited the formation of autophagolysosomes, which caused clustering of the LC3-II in cells. In conclusion, autophagy promoted by BTXA serves as a potential protective effect on ischemia/reperfusion injury.
ISSN	17920981
Journal	Experimental and Therapeutic Medicine
Volume Number	16
PubMed Central reference number	PMC6257827
Issue Number	6
PubMed reference number	30542387
e-ISSN	17921015
DOI	10.3892/etm.2018.6741
Language	English
Publisher	D.A. Spandidos
Publisher Date	2018-09-17
Access Restriction	Open
Rights License	This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. Copyright: © Shi et al.
Subject Keyword	autophagy botulinum toxin type A human dermal microvascular endothelial cells ischemia/reperfusion injury
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Cancer Research