ABSTRACT
Excessive use of alcohol is a serious problem in our society and induces various, severe alcohol related diseases. The cytotoxicities of ethanol are still largely unknown. We studied the molecular mechanisms of EtOH-induced SK-N-SH neuronal cell death and protective effects of baicalein and gramineus against EtOH-induced cytotoxicities. In our results, the cell death by EtOH showed morphologic features of apoptosis like as membrane blebbing, nuclear condensation and fragmentation. Furthermore, pretreated baicalein attenuated EtOH-induced neuronal cell death effectively. EtOH increased expression levels of p53 and both p53 antisense oligonucleotide and Pifithrin protected the cell death against EtOH. Also, EtOH induced mitochondrial event, collapse of mitochondrial membrane potential ( delta psi m ) and caspase cascade as a downstream of mitochondria. Interestingly, baicalein decreased expression levels of p53 and inhibited collapse of mitochondrial membrane potential. These results suggest that baicalein reduces mitochondrial dysfunction induced by EtOH through down-regulation of p53 expression levels. Also, baicalein attenuated activation of caspase, which was triggered by mitochondrial malfunction. But gramineus didn't have any protective effect. These results imply that baicalein significantly protects EtOH-induced neuronal cell death through regulating p53, mitochondrial dysfunction and caspase activation.
Subject(s)
Apoptosis , Blister , Cell Death , Down-Regulation , Ethanol , Membrane Potential, Mitochondrial , Membranes , Mitochondria , Neurons , Signal TransductionABSTRACT
Excessive use of alcohol is a serious problem in our society and induces various, severe alcohol related diseases. The cytotoxicities of ethanol are still largely unknown. We studied the molecular mechanisms of EtOH-induced SK-N-SH neuronal cell death and protective effects of baicalein and gramineus against EtOH-induced cytotoxicities. In our results, the cell death by EtOH showed morphologic features of apoptosis like as membrane blebbing, nuclear condensation and fragmentation. Furthermore, pretreated baicalein attenuated EtOH-induced neuronal cell death effectively. EtOH increased expression levels of p53 and both p53 antisense oligonucleotide and Pifithrin protected the cell death against EtOH. Also, EtOH induced mitochondrial event, collapse of mitochondrial membrane potential ( delta psi m ) and caspase cascade as a downstream of mitochondria. Interestingly, baicalein decreased expression levels of p53 and inhibited collapse of mitochondrial membrane potential. These results suggest that baicalein reduces mitochondrial dysfunction induced by EtOH through down-regulation of p53 expression levels. Also, baicalein attenuated activation of caspase, which was triggered by mitochondrial malfunction. But gramineus didn't have any protective effect. These results imply that baicalein significantly protects EtOH-induced neuronal cell death through regulating p53, mitochondrial dysfunction and caspase activation.