Vitamin A bio-modulates apoptosis via the mitochondrial pathway after hypoxic-ischemic brain damage

Autor: Ping Qu, Yang Bi, Tingyu Li, Min Guo, Jie Chen, Yun Zhang, Yuan Shi, Min Gong, Wei Jiang, Li Chen, Youxue Liu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Retinoic acid
Apoptosis
Pharmacology
Hippocampus
lcsh:RC346-429
Rats
Sprague-Dawley
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
0302 clinical medicine
Vitamin A (VA)
Retinoic acid (RA)
Vitamin A
Cells
Cultured
Spatial Memory
bcl-2-Associated X Protein
Membrane Potential
Mitochondrial
Neurons
Vitamin A Deficiency
Retinoic Acid Receptor alpha
Mitochondria
Caspases
Mitochondrial membrane potential (MMP)
Hypoxia-Ischemia
Brain
Female
medicine.symptom
Signal transduction
Signal Transduction
Tretinoin
Brain damage
Neuroprotection
03 medical and health sciences
Cellular and Molecular Neuroscience
In vivo
medicine
Animals
Learning
RNA
Messenger
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
lcsh:Neurology. Diseases of the nervous system
PI3K/Akt
business.industry
Research
Oxygen
Glucose
030104 developmental biology
chemistry
Dietary Supplements
Hypoxic-ischemic brain damage (HIBD)
business
Proto-Oncogene Proteins c-akt
030217 neurology & neurosurgery
Zdroj: Molecular Brain, Vol 11, Iss 1, Pp 1-16 (2018)
Molecular Brain
ISSN: 1756-6606
Popis: Our previous studies demonstrated that vitamin A deficiency (VAD) can impair the postnatal cognitive function of rats by damaging the hippocampus. The present study examined the effects of retinoic acid (RA) on apoptosis induced by hypoxic-ischemic damage in vivo and in vitro, and investigated the possible signaling pathway involved in the neuroprotective anti-apoptotic effects of RA. Flow cytometry, immunofluorescence staining and behavioral tests were used to evaluate the neuroprotective and anti-apoptotic effects of RA. The protein and mRNA levels of RARα, PI3K, Akt, Bad, caspase-3, caspase-8, Bcl-2, Bax, and Bid were measured with western blotting and real-time PCR, respectively. We found impairments in learning and spatial memory in VAD group compared with vitamin A normal (VAN) and vitamin A supplemented (VAS) group. Additionally, we showed that hippocampal apoptosis was weaker in the VAN group than that in VAD group. Relative to the VAD group, the VAN group also had increased mRNA and protein levels of RARα and PI3K, and upregulated phosphorylated Akt/Bad levels in vivo. In vitro, excessively low or high RA signaling promoted apoptosis. Furthermore, the effects on apoptosis involved the mitochondrial membrane potential (MMP). These data support the idea that sustained VAD following hypoxic-ischemic brain damage (HIBD) inhibits RARα, which downregulates the PI3K/Akt/Bad and Bcl-2/Bax pathways and upregulates the caspase-8/Bid pathway to influence the MMP, ultimately producing deficits in learning and spatial memory in adolescence. This suggests that clinical interventions for HIBD should include suitable doses of VA. Electronic supplementary material The online version of this article (10.1186/s13041-018-0360-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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