Nigericin-induced Impairment of Autophagic Flux in Neuronal Cells Is Inhibited by Overexpression of Bak
- Authors
- Lim, Junghyun; Lee, Yunsu; Kim, Hyun-Wook; Rhyu, Im Joo; Oh, Myung Sook; Youdim, Moussa B. H.; Yue, Zhenyu; Oh, Young J.
- Issue Date
- 6-7월-2012
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- BCL-2 FAMILY-MEMBERS; MULTIVESICULAR BODIES; CATION COMPLEXES; MAMMALIAN-CELLS; X-L; APOPTOSIS; PROTEIN; DEATH; BECLIN-1; MACROAUTOPHAGY
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.287, no.28, pp.23271 - 23282
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 287
- Number
- 28
- Start Page
- 23271
- End Page
- 23282
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/107943
- DOI
- 10.1074/jbc.M112.364281
- ISSN
- 0021-9258
- Abstract
- Bak is a prototypic pro-apoptotic Bcl-2 family protein expressed in a wide variety of tissues and cells. Recent studies have revealed that Bcl-2 family proteins regulate apoptosis as well as autophagy. To investigate whether and how Bak exerts a regulatory role on autophagy-related events, we treated independent cell lines, including MN9D neuronal cells, with nigericin, a K+/H+ ionophore. Treatment of MN9D cells with nigericin led to an increase of LC3-II and p62 levels with concomitant activation of caspase. Ultrastructural examination revealed accumulation of autophagic vacuoles and swollen vacuoles in nigericin-treated cells. We further found that the LC3-II accumulated as a consequence of impaired autophagic flux and the disrupted degradation of LC3-II in nigericin-treated cells. In this cell death paradigm, both transient and stable overexpression of various forms of Bak exerted a protective role, whereas it did not inhibit the extent of nigericin-mediated activation of caspase-3. Subsequent biochemical and electron microscopic studies revealed that overexpressed Bak maintained autophagic flux and reduced the area occupied by swollen vacuoles in nigericin-treated cells. Similar results were obtained in nigericin-treated non-neuronal cells and another proton ionophore-induced cell death paradigm. Taken together, our study indicates that a protective role for Bak during ionophore-induced cell death may be closely associated with its regulatory effect on maintenance of autophagic flux and vacuole homeostasis.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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