The Change of Mitochondrial Membrane Potential during Dolichyl Phosphate-Induced Apoptosis in Human Monoblastic Leukemia U937 Cells

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Mitochondria play important roles in apoptosis process. Liberation of cytochrome C and AIF (Apoptosis-Inducing Factor) located mitochondrial innermembrane activates downstream caspases and accelerates apoptosis. In previous study, we found that dolichyl phosphate (DOL-P), an essential carrier lipid in the biosynthesis of N-linked glycoprotein, induced apoptosis in rat glioma C6 cells, human myeloblastic leukemia HL-60 cells, and human monoblastic leukemia U937 cells. Apoptotic phenomena on DOL-P-induced apoptosis, such as nuclear chromatin condensation, increase of plasma membrane fluidity, activation of caspase 3-like protease, translocation phosphatidylserine and phosphatidylethanolamine from inner to outer plasma membrane, have been found. Here, we investigate relationship between change of mitochondrial membrane potential (⊿Ψm) and DNA fragmentation during DOL-P-induced apoptosis in U937 cells. The loss of ⊿Ψm occurred 1h after treatment. Both specific inhibitors of caspase 3,acetyl-Asp-Glu-Val-Asp-aldehyde (DEVD-CHO) and caspase 8,acetyl-Ile-Glu-Thr-Asp-aldehyde (IETD-CHO) could not inhibit the loss of ⊿Ψm. In contrast, DNA fragmentation occurred 3h after treatment and was inhibited by DEVD-CHO and IETD-CHO. Based on these results, we propose the following sequence of apoptotic pathway induced by DOL-P, the increase of plasma membrane fluidity, loss of ⊿Ψm, caspase activation and DNA fragmentaion.
東海大学の論文