Metabolic and Genetic Analyses of Apoptosis in Potassium/Serum-Deprived Rat Cerebellar Granule Cells
Open accessAbstract
Cerebellar granule cells maintained in medium containing serum and 25 m m potassium undergo an apoptotic death within 96 hr when switched to serum-free medium with 5 m m potassium. Because large numbers of apparently homogeneous neurons can be obtained, this represents a potentially useful model of neuronal programmed cell death (PCD). Analysis of the time course and extent of death after removal of either serum or K+alone demonstrated that a fast-dying (T1/2= 4 hr) population (20%) responded to serum deprivation, whereas a slow-dying (T1/2= 25 hr) population (80%) died in response to K+deprivation. Taking advantage of the complete death after removing both K+and serum, changes in metabolic events and mRNA levels were analyzed in this model. Glucose uptake, protein synthesis, and RNA synthesis fell to <35% of control by 9 hr after potassium/serum deprivation, a time when 85% of the cells were still viable. The pattern of the fall in these metabolic parameters was similar to that reported for trophic factor-deprived sympathetic neurons. Most mRNAs decreased markedly after K+/serum deprivation. Levels of c-jun mRNA increased fivefold in potassium/serum-deprived granule cells;c-jun is required for cell death of sympathetic neurons. mRNA levels of cyclin D1,c-myb,collagenase, and transin remained relatively constant in potassium/serum-deprived granule cells. These data demonstrate the existence of two populations of granule cells with respect to cell death and define common metabolic and genetic events involved in neuronal PCD.
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The point-of-no-return for CGN apoptosis takes place within the first 6 h of deprivation, and onset of apoptosis can be observed at 6 h post-deprivation by phosphorylation of c-Jun and activation of caspase-3.
“The point-of-no-return for the CGN apoptosis takes place within the first 6 h of deprivation, and the onset of apoptosis can be observed at 6 h postdeprivation by phosphorylation of c-Jun, the central transcription factor required for JNK-dependent apoptosis, and activation of caspase-3, a major executioner of apoptosis [22,26,27].”
From PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling (2012) · cites this paper as [22]
In “Loss of cell viability and K⁺/serum rescue” (page not available), the paper places the commitment point—when 50% of cells can no longer be rescued—at approximately 12 hours, not within the first 6 hours. “Analysis of gene expression” reports increased c-jun mRNA by 3 hours, but does not establish apoptosis onset at 6 hours through c-Jun phosphorylation or caspase-3 activation. (LLM, conf=0.88)
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- Estus S (1996) Optimization and validation of RT-PCR as a tool to analyze apoptotic gene expression. In: NeuroMethods (Poirier J, ed). New York: Elsevier, in press.
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- Authors
- Miller, T. M., & Johnson Jr., E. M.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- Miller, Timothy M.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1996-12-01
- Volume
- 16
- Issue
- 23
- Pages
- 7487-7495
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6579076
- OpenAlex
- W2125779862
- Cited by
- 228
- References
- 0
- Citations by year
- 2024: 2 · 2022: 1 · 2020: 14 · 2019: 2 · 2018: 1 · 2017: 1 · 2015: 1 · 2014: 2 · 2012: 5
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R37AG012947, AG-12947)
- National Institute of Neurological Disorders and Stroke (NS 24679, R01NS024679)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- apoptosis, cerebellar granule cells, potassium deprivation, serum deprivation, glucose uptake, protein synthesis, RNA synthesis, mRNA levels, trophic factor deprivation, sympathetic neurons
- MeSH terms
- Animals, Blood Physiological Phenomena, Cell Survival, Cells, Cultured, Cerebellum, Potassium, Potassium Deficiency, Gene Expression, Culture Media, Serum-Free, Rats, Sprague-Dawley, Apoptosis, Rats
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