The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Induction of the Intrinsic Apoptotic Pathway by 3-Deazaadenosine Is Mediated by BAX Activation in HL-60 Cells

  • Lee, Sun-Young (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Ko, Kyoung-Won (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Kang, Won-Kyung (Department of Surgery, College of Medicine, The Catholic University of Korea) ;
  • Choe, Yun-Jeong (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Kim, Yoon-Hyoung (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Kim, In-Kyung (Department of Biochemistry, College of Medicine, The Catholic University of Korea) ;
  • Kim, Jin (Department of Anatomy, College of Medicine, The Catholic University of Korea) ;
  • Kim, Ho-Shik (Department of Biochemistry, College of Medicine, The Catholic University of Korea)
  • Received : 2010.11.01
  • Accepted : 2010.11.17
  • Published : 2010.12.31
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Abstract

3-Deazaadenosine (DZA), a potent inhibitor of S-adenosylhomocysteine hydrolase, was previously proposed to induce intrinsic apoptosis in human leukemic cells. In the present study, we analyzed the mechanism underlying the DZA-induced intrinsic apoptotic pathway. DZA activated typical caspase-dependent apoptosis in HL-60 cells, as demonstrated by an accumulation of hypo-diploidic cells, the processing of multiple procaspases and an inhibitory effect of z-VAD-Fmk on this cell death. During DZA-induced apoptosis, cytochrome c (cyt c) was released into the cytosol. This was neither prevented by z-VAD-Fmk and nor was it associated with the dissipation of mitochondrial membrane potential (${\Delta}{\Psi}_m$). Prior to the release of cyt c, BAX was translocated from the cytosol to mitochondria and underwent oligomerization. Finally, the overexpression of BCL-XL protected HL-60 cells from apoptosis by blocking both the cyt c release and BAX oligomerization. Collectively, these findings suggest that DZA may activate intrinsic apoptosis by stimulating BAX activation and thereby the release of cyt c.

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References

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