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Anthocyanins protect against ethanol-induced neuronal apoptosis via GABAB1 receptors intracellular signaling in prenatal rat hippocampal neurons.
- Source :
-
Molecular neurobiology [Mol Neurobiol] 2013 Aug; Vol. 48 (1), pp. 257-69. Date of Electronic Publication: 2013 May 04. - Publication Year :
- 2013
-
Abstract
- Here, we investigated the possible involvement of gamma-aminobutyric acid B1 receptor (GABAB1R) in mediating the protective effects of black soybean anthocyanins against ethanol-induced apoptosis in prenatal hippocampal neurons because GABARs are known to play an important role in the development of central nervous system. Treatments were performed on primary cultures of prenatal rat hippocampal neurons transfected with or without GABAB1R small interfering RNA (siRNA). The results showed that, when ethanol treatment was followed by anthocyanins treatment, cellular levels of proapoptotic proteins such as Bax, activated caspase-3, and cleaved poly (ADP-ribose) polymerase 1 (PARP-1) were decreased, and the cellular level of the antiapoptotic protein Bcl-2 was increased compared to treatment with ethanol alone. Furthermore, the effects of ethanol on cellular levels of GABAB1R and its downstream signaling molecules such as protein kinase A, calcium/calmodulin-dependent protein kinase II (CaMKII), and phosphorylated cAMP response element binding protein were diminished or reversed by anthocyanins treatment. The ability of anthocyanins to reverse the effects of ethanol on cellular levels of Bax, Bcl-2, active caspase-3, cleaved PARP-1, GABAB1R, and CaMKII were abrogated in cells transfected with GABAB1R siRNA. In a GABAB1R-dependent manner, anthocyanins also inhibited the ability of ethanol to elevate intracellular free Ca(2+) level and increase the proportion of cells with low mitochondrial membrane potential in the population. Cell apoptosis assay and morphological studies also confirmed the neuroprotective effect of anthocyanins against ethanol via GABAB1R. Our data suggest that GABAB1R plays an important role in the neuroprotective effects of anthocyanins against ethanol.
- Subjects :
- Animals
Biomarkers metabolism
Calcium metabolism
Cell Shape drug effects
Ethanol
Female
Fetus drug effects
Fetus metabolism
Hippocampus embryology
Homeostasis drug effects
Intracellular Space drug effects
Intracellular Space metabolism
Membrane Potential, Mitochondrial drug effects
Nerve Degeneration pathology
Neurons drug effects
Neurons pathology
Rats
Rats, Sprague-Dawley
Anthocyanins pharmacology
Apoptosis drug effects
Hippocampus pathology
Neurons metabolism
Neuroprotective Agents pharmacology
Receptors, GABA-B metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1182
- Volume :
- 48
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular neurobiology
- Publication Type :
- Academic Journal
- Accession number :
- 23645118
- Full Text :
- https://doi.org/10.1007/s12035-013-8458-y