Korean J Phys Anthropol.  2006 Mar;19(1):49-59.

Study on the Mitochondrial Dysfunction by p53 Regulation in Ceramide-induced Neuronal Cell Death

• Lee DY
• Lee HJ
• Noh YH
• Yun JY
• Han IS
• Chung YH
• Kim KY
• Kim SS
• Lee WB

Abstract

Ceramide induces cell death in a dose- and time-dependent manner in neuroblastoma SK-N-SH cells. To investigate the mechanism of SK-N-SH cell death by C2-ceramide, morphological features and Hoechst 33258 staining were analyzed. In these morphlogic study the cell death by ceramide showed typical apoptotic features, nuclear condensation, fragmentation, and membrane blebbing. Ceramide-induced apoptosis was accompanied by nuclear accumulation of p53. Inhibition of p53 expression with p53 antisense oligonucleotides inhibited apoptosis evoked by ceramide. Also, ceramide induced mitochondrial event, collapse of mitochondrial membrane potential (delta psi m) and interestingly, inhibition of p53 attenuated collapse of mitochondrial membrane potential, suggests that ceramide induces mitochondrial dysfunction through upregulation of p53 expression. These results suggest that ceramide-induced apoptosis is dependent upon increase in cellular p53 levels which play a critical role in the regulation of apoptotic cell death and p53 modulates mitochondrial function such as mitochondrial membrane potential level.

Keyword

Ceramide; Apoptosis; SK-N-SH; p53; Mitochondrial membrane potential (MMP)

MeSH Terms

Apoptosis
Bisbenzimidazole
Blister
Cell Death*
Membrane Potential, Mitochondrial
Membranes
Neuroblastoma
Neurons*
Oligonucleotides, Antisense
Up-Regulation
Bisbenzimidazole
Oligonucleotides, Antisense