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- Title
Restoring Pharmacologic Preconditioning in the Aging Heart: Role of Mitophagy/Autophagy.
- Authors
Li Ma; Jiang Zhu; Qun Gao; Rebecchi, Mario J.; Qiang Wang; Lixin Liu; Ma, Li; Zhu, Jiang; Gao, Qun; Wang, Qiang; Liu, Lixin
- Abstract
We previously reported that pretreatment with the potent antioxidant TEMPOL improves mitochondrial function and restores preconditioning in the aging heart. Because mitophagy is implicated in cardiac preconditioning and declines with age, this study was designed to investigate how age influences mitophagy in response to preconditioning and whether TEMPOL pretreatment improves it. Old (22-24 months) rats were pretreated with or without 4-week TEMPOL and compared with young (4-6 months) untreated rats. Cardioprotection induced by isoflurane (ISO) in vivo and in isolated cardiomyocytes in vitro was assessed following ischemia/reperfusion and simulated hypoxia/reoxygenation, respectively. Mitophagy was determined by comparing the levels/subcellular locations of key mitophagic markers using Western blotting and immunofluorescence techniques. ISO preconditioned the young but not old heart in vivo and in vitro. Aging impaired ISO-induced mitochondrial accumulation of PINK1 and Parkin, as well as mitochondrial ubiquitination, and baseline and ISO-induced autophagic flux assessed by LC3 puncta, membrane associated LC3-II and p62. Pretreatment with TEMPOL improved these processes and restored ISO preconditioning. Inhibition of autophagy abolished ISO-induced protection in cardiomyocytes from young and TEMPOL pretreated old rats. Thus, antioxidant pretreatment significantly improves mitophagic response to ISO in old myocardium, which may contribute to restoration of cardioprotection in senescent animals.
- Subjects
TEMPOL; AUTOPHAGY; CARDIOTONIC agents; WESTERN immunoblotting; IMMUNOFLUORESCENCE; TREATMENT of cardiomyopathies; UBIQUITINATION; HEART physiology; AGING; ANESTHESIA; ANIMAL experimentation; ANTIOXIDANTS; CELLS; FREE radicals; HEART; ISOFLURANE; MITOCHONDRIA; OXIDES; RATS; INHALATION anesthetics; PHARMACODYNAMICS
- Publication
Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2017, Vol 72, Issue 4, p489
- ISSN
1079-5006
- Publication type
journal article
- DOI
10.1093/gerona/glw168