title: Hydroxychloroquine attenuates cigarette smoke induced autophagic signaling in the mouse ovary.
abstract: We previously demonstrated that Cigarette Smoke (CS) induces autophagy in the ovary. Therefore we aimed to determine if chloroquine (CQ) could inhibit CS-induced autophagy in the ovary. Eight week old mice were implanted with CQ pellets; 0, 25, and 50mg CQ/kg. Half of the animals in each group were exposed to room air and the other half were exposed to CS twice daily for 8 weeks. Ovaries were harvested for electron microscopy, gene and protein expression analysis. There was a significant increase in the production of autophagosomes in granulosa cells of mice exposed to CS (p=0.0297). However 25 and 50mg/kg CQ treatment significantly decreased the CS-induced autophagosomes (p=0.0505; p=0.0065) and attenuated the effects of CS on LC3B and BECN1 expression. In summary, this suggests that CQ attenuates CS-induced autophagy in the ovary and that ovarian protection from toxic insult is potentially feasible.
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: H C
authors.initials: HC
authors.lastname: Furlong
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Wessels
authors.affiliation: Institute of Biosciences, UNESP-Univ Estadual Paulista, Department of Morphology, Botucatu, São Paulo, Brazil.
authors.forename: M T
authors.initials: MT
authors.lastname: Guerra
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
authors.forename: M R
authors.initials: MR
authors.lastname: Stämpfli
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario L8N 3Z5, Canada. Electronic address: foster@mcmaster.ca.
authors.forename: W G
authors.initials: WG
authors.lastname: Foster
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D000071186:Beclin-1 / Q000235:genetics / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006886:Hydroxychloroquine / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020011:Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D062789:Tobacco Products / Q000009:adverse effects*
chemical_list: D000071186:Beclin-1; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D020011:Protective Agents; D012906:Smoke; D006886:Hydroxychloroquine
keywords: Autophagy; Cell death; Cigarette smoke; Ovarian function