机构:[1]Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA[2]Department of Anesthesia, Beijing Tongren Hospital, Capital Medical University, Beijing, China临床科室麻醉科首都医科大学附属北京同仁医院首都医科大学附属同仁医院[3]Department of Forensic Pathology, Faculty of Forensic Medicine, China Medical University, Shenyang, China[4]Department of Anesthesia, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
Commonly used anesthetic isoflurane has been reported to promote Alzheimer's disease (AD) neuropathogenesis by inducing caspase-3 activation. However, the up-stream mechanisms of isoflurane's effects remain largely to be determined. Specifically, there is a lack of a good model/system to elucidate the underlying mechanism of the isoflurane-induced caspase-3 activation. We therefore set out to assess and compare the effects of isoflurane on caspase-3 activation in neural progenitor cells (NPCs) and in primary neurons from wild-type (WT) and AD transgenic (Tg) mice. The NPCs and neurons were obtained, cultured and then treated with either 2% isoflurane or under control condition for 6 h. The NPCs or neurons were harvested at the end of the treatment and were subjected to Western blot analysis. Here we showed for the first time that the isoflurane treatment induced caspase-3 activation in neurons, but not in NPCs, from either WT or AD Tg mice. Consistently, the isoflurane treatment increased cytosol levels of cytochrome c, a potential up stream mechanism of isoflurane-induced caspase-3 activation in the mice neurons, but not NPCs. Finally, the isoflurane treatment induced a greater casapse-3 activation in the neurons, but not the NPCs, from AD Tg mice as compared to the WT mice. These data demonstrated that investigation and comparison of isoflurane's effects between mice NPCs and neurons would serve as a model/system to determine the underlying mechanism by which isoflurane induces caspase-3 activation. These findings would promote more research to investigate the effects of anesthetics on AD neuropathogenes s and the underlying mechanisms.
基金:
National Institutes of Health, Bethesda, MarylandUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21AG038994, R01 GM088801, R01 AG041274]; Alzheimer's Association, Chicago, IllinoisAlzheimer's Association; Cure Alzheimer's Fund, Wellesley, Massachusetts; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [R01GM088801] Funding Source: NIH RePORTER; NATIONAL INSTITUTE ON AGINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG041274] Funding Source: NIH RePORTER
第一作者机构:[1]Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA
共同第一作者:
通讯作者:
通讯机构:[1]Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA[*1]Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 4310, Charlestown, MA 02129-2060, USA
推荐引用方式(GB/T 7714):
Yiying Zhang,Chuxiong Pan,Xu Wu,et al.Different effects of anesthetic isoflurane on caspase-3 activation and cytosol cytochrorne mice levels between m neural progenitor cells and neurons[J].FRONTIERS IN CELLULAR NEUROSCIENCE.2014,8:doi:10.3389/fncel.2014.00014.
APA:
Yiying Zhang,Chuxiong Pan,Xu Wu,Yuanlin Dong,Deborah J. Culley...&Zhongcong Xie.(2014).Different effects of anesthetic isoflurane on caspase-3 activation and cytosol cytochrorne mice levels between m neural progenitor cells and neurons.FRONTIERS IN CELLULAR NEUROSCIENCE,8,
MLA:
Yiying Zhang,et al."Different effects of anesthetic isoflurane on caspase-3 activation and cytosol cytochrorne mice levels between m neural progenitor cells and neurons".FRONTIERS IN CELLULAR NEUROSCIENCE 8.(2014)