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Neuroprotective effects of Activin A on endoplasmic reticulum stress-mediated apoptotic and autophagic PC12 cell death
- Source :
- Neural Regeneration Research, Vol 12, Iss 5, Pp 779-786 (2017), Neural Regeneration Research
- Publication Year :
- 2017
- Publisher :
- Wolters Kluwer Medknow Publications, 2017.
-
Abstract
- Activin A, a member of the transforming growth factor-beta superfamily, plays a neuroprotective role in multiple neurological diseases. Endoplasmic reticulum (ER) stress-mediated apoptotic and autophagic cell death is implicated in a wide range of diseases, including cerebral ischemia and neurodegenerative diseases. Thapsigargin was used to induce PC12 cell death, and Activin A was used for intervention. Our results showed that Activin A significantly inhibited morphological changes in thapsigargin-induced apoptotic cells, and the expression of apoptosis-associated proteins [cleaved-caspase-12, C/EBP homologous protein (CHOP) and cleaved-caspase-3] and biomarkers of autophagy (Beclin-1 and light chain 3), and downregulated the expression of thapsigargin-induced ER stress-associated proteins [inositol requiring enzyme-1 (IRE1), tumor necrosis factor receptor-associated factor 2 (TRAF2), apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38]. The inhibition of thapsigargin-induced cell death was concentration-dependent. These findings suggest that administration of Activin A protects PC12 cells against ER stress-mediated apoptotic and autophagic cell death by inhibiting the activation of the IRE1-TRAF2-ASK1-JNK/p38 cascade.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Programmed cell death
autophagy
Thapsigargin
p38 mitogen-activated protein kinases
p38
Biology
lcsh:RC346-429
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Developmental Neuroscience
Internal medicine
nerve regeneration
Activin A
endoplasmic reticulum stress
apoptosis
c-Jun N-terminal kinase
neural regeneration
medicine
ASK1
lcsh:Neurology. Diseases of the nervous system
Endoplasmic reticulum
Autophagy
Cell biology
030104 developmental biology
Endocrinology
chemistry
Apoptosis
Tumor necrosis factor alpha
030217 neurology & neurosurgery
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 16735374
- Volume :
- 12
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Neural Regeneration Research
- Accession number :
- edsair.doi.dedup.....00741861110b74d8b222dacdddb48641