ABSTRACT
Apoptosis manifests in two major execution programs downstream of the death signal: the caspase pathway and organelle dysfunction. An important antiapoptosis factor, Bcl-2 protein, contributes in caspase pathway of apoptosis. Calcium, an important intracellular signal element in cells, is also observed to have changes during apoptosis, which maybe affected by Bcl-2 protein. We have previously reported that in Harringtonine (HT) induced apoptosis of HL-60 cells, there's a change of intracellular calcium distribution, moving from cytoplast especially Golgi's apparatus to nucleus and accumulating there with the highest concentration. We report here that caspase-3 becomes activated in HT-induced apoptosis of HL-60 cells, which can be inhibited by overexpression of Bcl-2 protein. No sign of apoptosis or intracellular calcium movement from Golgi's apparatus to nucleus in HL-60 cells overexpressing Bcl-2 or treated with Ac-DEVD-CHO, a specific inhibitor of caspase-3. The results indicate that activated caspase-3 can promote the movement of intracellular calcium from Golgi's apparatus to nucleus, and the process is inhibited by Ac-DEVD-CHO (inhibitor of caspase-3), and that Bcl-2 can inhibit the movement and accumulation of intracellular calcium in nucleus through its inhibition on caspase-3. Calcium relocalization in apoptosis seems to be irreversible, which is different from the intracellular calcium changes caused by growth factor.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
White E . Life, death and pursuit of apoptosis Genes Dev 1996; 10:1–15.
Wyllie AH . glucocorticoid induced thymocyte apoptosis is associated with endogeneous endonuclease activation. Nature 1980; 284:555–6.
Yuan JY, Shaham S, Ledoux S, Ellis MH, Horvitz RH . The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1b converting enzyme. Cell 1993; 75:641–52.
Alnemri ES, Livingston DJ, Nichoison DW, Salvesen G, Thornberry NA, Wong WW . Human ICE/CED-3 protease nomenclature. Cell 1996; 87:171.
Nicholson WD, Ali A, Thornberry NA, et al. Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature 1995; 376:37–43.
Ibrado AM, Huang Y, Fang G, Liu L, Bhalla K . Overexpression of Bcl-2 or Bcl-XL inhibits Ara-C-induced CPP32/Yama protease activity and apoptosis of human acute myelogenous leukemia HL-60 cells. Cancer Res. 1996; 56:4743–8.
Armstrong RC, Aja T, Xiang J, Gaur S, Krebs JF, Hoang K, Bai X, Korsmeyer SJ, Karanewsky DS, Fritz LC, Tomaselli KJ . Fas-induced activation of the cell death-related protease CPP32 is inhibited by Bcl-2 and by ICE family protease inhibitors. J Biol Chem 1996; 271:16850–5.
Chinnaiyan AM, Orth K, O'rourke K, Duan H, Poirier GG, dixit BM . Molecular ordering of the cell death pathway. Bcl-2 and Bcl-xL function upstream of the CED-3 like apoptotic proteases. J Biol Chem 1996; 271:4573–6.
Fang M, Zhang HQ, Xue SB, et al. Intracellular calcium distribution in apoptosis of HL-60 cells induced by harringtonine: intranuclear accumulation and regionalization. Cancer Lett 1998; 127(1-2):113–21.
Cui J, Yan L, Shaobai Xue . Visualization of Golgia apparatus as an intracellular calcium store by laser scanning confocal microscope. Cell Res 1995; 5:165–79.
McConkey DJ Orrenius S . The role of calcium in the regulation of apoptosis. J Leukocyte Biol 1996; 59:775–83.
Nath R, Raser KJ, Hajimohammadreza I, Wang KKW . Thapsigargin induces apoptosis in SH-SY5Y neuroplastoma cells and cerebrocortical cultures. Biochem Mol Int 1997; 43(1):197–205.
Kruman II, Mattson MP . Pivotal role of mitochondria calcium uptake in neural cell apoptosis and necrosis. J Neurochem 1999; 72(2):529–40.
Lam M, Dubyak G, distelhorst XW . Effect of glucocorticoid treatment on intracellular calcium homeostasis in mouse lymphoma cells. Mol Endocrinol 1993; 269:365–70.
Chakraborti T, Ghosh SK, Michael JR, Batabyal SK, Chakraborti S . Mol. Targets of oxidative stress in cardiovascular system. Cell Biochem 1998; 187(1-2):1–10.
Walker PR, Sikorska m . New aspects of the mechanism of DNA fragmentation in apoptosis. Biolchem Cell biol 1997; 75(4):287–99.
Makrigiannis AP, Hoskin SW . Cyclosporin A inhibits 2-chloroadenosine-induced DNA cleavage in mouse thymocytes.Int J Immunopharmacol 1994; 16:995–1001.
Kruman I, Guo Q, Mattson MP . Calcium and reactive oxygen species mediate staurosporine-induced mitochondria dysfunction and apoptosis in PC12 cells. J Neurosci Res 1998; 51(3):293–308.
Acknowledgements
We thank Dr. WANG Xiao Dong (University of Texas Southwestern Medical Center, USA) for his advice and help. We thank Professor LI Shu Wen for her kindly help. Project supported by the National Natural Science Foundation of China (Grant No. 39730160).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
ZHANG, M., ZHANG, H. & XUE, S. Effect of Bcl-2 and caspase-3 on calcium distribution in apoptosis of HL-60 cell. Cell Res 10, 213–220 (2000). https://doi.org/10.1038/sj.cr.7290050
Received:
Revised:
Accepted:
Issue date:
DOI: https://doi.org/10.1038/sj.cr.7290050
Keywords
This article is cited by
-
MicroRNA-21 promotes proliferation, invasion and suppresses apoptosis in human osteosarcoma line MG63 through PTEN/Akt pathway
Tumor Biology (2016)
-
Programmed cell death of secretory cavity cells of citrus fruits is associated with Ca2+ accumulation in the nucleus
Trees (2014)
-
Coxsackievirus B3-induced apoptosis and Caspase-3
Cell Research (2003)
-
Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression
Cell Research (2003)
