Back to Search
Start Over
Varying butyric acid amounts induce different stress- and cell death-related signals in nerve growth factor-treated PC12 cells: implications in neuropathic pain absence during periodontal disease progression
- Source :
- Apoptosis. 21:699-707
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Neuropathic pain is absent from the early stages of periodontal disease possibly due to neurite retraction. Butyric acid (BA) is a periodontopathic metabolite that activates several stress-related signals and, likewise, induce neurite retraction. Neuronal cell death is associated to neurite retraction which would suggest that BA-induced neurite retraction is ascribable to neuronal cell death. However, the underlying mechanism of BA-related cell death signaling remains unknown. In this study, we exposed NGF-treated PC12 cells to varying BA concentrations [0 (control), 0.5, 1.0, 5.0 mM] and determined selected stress-related (H2O2, glutathione reductase, calcium (Ca(2+)), plasma membrane Ca(2+) ATPase (PMCA), and GADD153/CHOPS) and cell death-associated (extrinsic: FasL, TNF-α, TWEAK, and TRAIL; intrinsic: cytochrome C (CytC), NF-kB, CASP8, CASP9, CASP10, and CASP3) signals. Similarly, we confirmed cell death execution by chromatin condensation. Our results showed that low (0.5 mM) and high (1.0 and 5.0 mM) BA levels differ in stress and cell death signaling. Moreover, at periodontal disease-level BA concentration (5 mM), we observed that only FasL amounts were affected and occurred concurrently with chromatin condensation insinuating that cells have fully committed to neurodegeneration. Thus, we believe that both stress and cell death signaling in NGF-treated PC12 cells are affected differently depending on BA concentration. In a periodontal disease scenario, we hypothesize that during the early stages, low BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurite non-proliferation, whereas, during the later stages, high BA amounts accumulate resulting to both stress- and cell death-related signals that favor neurodegeneration. More importantly, we propose that neuropathic pain absence at any stage of periodontal disease progression is ascribable to BA accumulation regardless of amount.
- Subjects :
- 0301 basic medicine
Cancer Research
Programmed cell death
Neurite
Clinical Biochemistry
Cell
Pharmaceutical Science
Apoptosis
Biology
medicine.disease_cause
PC12 Cells
03 medical and health sciences
0302 clinical medicine
Nerve Growth Factor
Neurites
medicine
Animals
Periodontal Diseases
Pharmacology
Biochemistry (medical)
Neurodegeneration
Cell Biology
medicine.disease
Rats
Cell biology
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
Nerve growth factor
Biochemistry
Disease Progression
Butyric Acid
Neuralgia
Signal transduction
Transcription Factor CHOP
030217 neurology & neurosurgery
Oxidative stress
Signal Transduction
Subjects
Details
- ISSN :
- 1573675X and 13608185
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Apoptosis
- Accession number :
- edsair.doi.dedup.....55a0b994a291c85f1c8d8e9e9a41b2a2