Korean J Phys Anthropol.  2004 Mar;17(1):31-43.

Studies on Signal Transduction Mechanism of Alcohol-induced Neuronal Cell Death and Protective Effect

• Lee DY
• Kim SS
• Kim KY
• Lee WB
• Kim DK
• Kim KH
• Jung HY
• Lee SH

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.

Keyword

Ethanol; Neuronal cell death; Baicalein; Gramineus; p53; Mitochondrial membrane potential (MMP) ; Caspase

MeSH Terms

Apoptosis
Blister
Cell Death*
Down-Regulation
Ethanol
Membrane Potential, Mitochondrial
Membranes
Mitochondria
Neurons*
Signal Transduction*
Ethanol