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The association of VDAC with cell viability of PC12 model of Huntington’s disease
- Source :
- Frontiers in Oncology, Vol 6 (2016), Frontiers in Oncology
- Publication Year :
- 2016
- Publisher :
- Frontiers Media S.A., 2016.
-
Abstract
- It is becoming increasingly apparent that mitochondria dysfunction plays an important role in the pathogenesis of Huntington’s disease (HD), but the underlying mechanism is still elusive. Thus, there is a still need for further studies concerning the upstream events in the mitochondria dysfunction that could contribute to cell death observed in HD. Taking into account the fundamental role of the voltage-dependent anion-selective channel (VDAC) in mitochondria functioning, it is reasonable to consider the channel as a crucial element in HD etiology. Therefore, we applied inducible PC12 cell model of HD to determine the relationship between the effect of expression of wild type and mutant huntingtin (Htt and mHtt, respectively) on cell survival and mitochondria functioning in intact cells under conditions of undergoing cell divisions. Because after 48 h of Htt and mHtt expression differences in mitochondria functioning co-occurred with differences in the cell viability, we decided to estimate the effect of Htt and mHtt expression lasted for 48 h on VDAC functioning. Therefore, we isolated VDAC from the cells and tested the preparations by black lipid membrane system. We observed that the expression of mHtt, but not Htt, resulted in changes of the open state conductance and voltage-dependence when compared to control cells cultured in the absence of the expression. Importantly, for all the VDAC preparations, we observed a dominant quantitative content of VDAC1, and the quantitative relationships between VDAC isoforms were not changed by Htt and mHtt expression. Thus, Htt and mHtt-mediated functional changes of VDAC, being predominantly VDAC1, which occur shortly after these protein appearances in cells, may result in differences concerning mitochondria functioning and viability of cells expressing Htt and mHtt. The assumption is important for better understanding of cytotoxicity as well as cytoprotection mechanisms of potential clinical application.
- Subjects :
- 0301 basic medicine
Cancer Research
Programmed cell death
congenital, hereditary, and neonatal diseases and abnormalities
Huntingtin
Voltage-dependent anion channel
Intact cells
Cell
Mitochondrion
lcsh:RC254-282
03 medical and health sciences
Huntington's disease
medicine
status of mitochondrial coupling
Viability assay
Original Research
biology
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Cell biology
Mitochondria
030104 developmental biology
medicine.anatomical_structure
Oncology
VDAC protein
biology.protein
VDAC1
Huntington’s disease
Subjects
Details
- Language :
- English
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Frontiers in Oncology
- Accession number :
- edsair.doi.dedup.....908de7a18355a8c6782474fb48b2b1bd
- Full Text :
- https://doi.org/10.3389/fonc.2016.00238/full