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http://dx.doi.org/10.5352/JLS.2010.20.12.1820

Endoplasmic Reticulum Stress Response and Apoptosis via the CoCl2-Induced Hypoxia in Neuronal Cells  

Kim, Seon-Hwan (Department of Neurosurgery, Chungnam National University School of Medicine)
Kwon, Hyon-Jo (Department of Neurosurgery, Chungnam National University School of Medicine)
Koh, Hyeon-Song (Department of Neurosurgery, Chungnam National University School of Medicine)
Song, Shi-Hun (Department of Neurosurgery, Chungnam National University School of Medicine)
Kwon, Ki-Sang (Department of Anatomy, Chungnam National University School of Medicine)
Kwon, O-Yu (Department of Anatomy, Chungnam National University School of Medicine)
Choi, Seung-Won (Department of Neurosurgery, Chungnam National University School of Medicine)
Publication Information
Journal of Life Science / v.20, no.12, 2010 , pp. 1820-1828 More about this Journal
Abstract
Cobalt(II) chloride, a chemical compound with the formula$CoCl_2$, has been widely used in the treatment of anemia, as a chemical agent for the induction of hypoxia in cell cultures, and is known to activate hypoxic signaling. However, excessive exposure to cobalt is associated with several clinical conditions, including asthma, pneumonia, and hematological abnormalities, and can lead to tissue and cellular toxicity. It is also known to induce apoptosis. One of the questions was that of whether $CoCl_2$ might induce apoptosis via endoplasmic reticulum (ER) stress in neurons. To address this question, first, the level of DNA fragmentation was measured for assay of apoptotic rates using $CoCl_2$ with neuron PC12 cells. After confirmation of apoptosis inductions, under the same conditions, the expression levels of ER stress associated factors [ER chaperones Bip, calnexin, ERp72, ERp29, PDI, and ER membrane kinases (IRE1, ATF6, PERK)] were examined by RT-PCR and Western blotting. These results indicated that apoptosis is induced through activation of ER membrane kinases via ER stress. In conclusion, during induction of apoptosis through $CoCl_2$-induced hypoxia in neuron PC12 cells, ER membrane kinase of IRE1 was dominantly up-expressed, and, consecutively, TRAF2, which has been suggested to be one of the links connecting apoptosis and ER stress, was strongly up-expressed.
Keywords
$CoCl_2$; apoptosis; hypoxia; endoplasmic reticulum (ER);
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1 Wang, G., T. K. Hazra, S. Mitra, H. M. Lee, and E. W. Englander. 2000. Mitochondrial DNA damage and a hypoxic response are induced by $CoCl(_2) $in rat neuronal PC12 cells. Nucleic Acids Res. 28, 2135-2140.   DOI
2 Mates, J. M., J. A. Segura, F. J. Alonso, and J. Marquez. 2006. Pathways from glutamine to apoptosis. Front Biosci. 11, 3164-3180   DOI
3 Mori, K. 2004. Unfolded protein response as a quality control mechanism of proteins. Tanpakushitsu Kakusan Koso 49, 992-997.
4 Ni, M. and A. S. Lee. 2007. ER chaperones in mammalian development and human diseases. FEBS Lett. 581, 3641- 3651.   DOI
5 Nishikawa, S., J. L. Brodsky, and K. Nakatsukasa. 2005. Roles of molecular chaperones in endoplasmic reticulum (ER) quality control and ER-associated degradation (ERAD). J. Biochem. 137, 551-555.   DOI
6 Przedborski, S. 2004. Programmed cell death in amyotrophic lateral sclerosis: a mechanism of pathogenic and therapeutic importance. Neurologist 10, 1-7.   DOI
7 Raven, J. F. and A. E. Koromilas. 2008. PERK and PKR: old kinases learn new tricks. Cell Cycle 7, 1146-1150.   DOI
8 Ron, D. and S. R. Hubbard. 2008. How IRE1 reacts to ER stress. Cell 132, 24-26.   DOI
9 Schroder, M. and R. J. Kaufman. 2006. Divergent roles of IRE1alpha and PERK in the unfolded protein response. Curr. Mol. Med. 6, 35-36.
10 Singh, S. and M. Dikshit. 2007. Apoptotic neuronal death in Parkinson's disease: involvement of nitric oxide. Brain Res. Rev. 54, 233-250.   DOI
11 Sun, Y. and Z. L. Peng. 2009. Programmed cell death and cancer. Postgrad. Med. J. 85, 134-140.   DOI
12 Bartolome, S., N. K. Dhillon, S. Buch, A. J. Casillan, J. G. Wood, and A. R. O'Brien-Ladner. 2009. Deferoxamine mimics the pattern of hypoxia-related injury at the microvasculature. Shock 31, 481-485.   DOI
13 Wang, Y., K. S. Lam, M. H. Yau, and A. Xu. 2008. Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem. J. 409, 623-633.   DOI
14 Yoshida, H. 2007. ER stress and diseases. FEBS J. 274, 630-658.   DOI
15 Zeno, S., M. Zaaroor, S. Leschiner, L. Veenman, and M. Gavish. 2009. $CoCl(_2) $ Induces Apoptosis via the 18 kDa Translocator Protein in U118MG Human Glioblastoma Cells. Biochemistry 48, 4652-4661.   DOI   ScienceOn
16 Zhao, L. and S. L. Ackerman. 2006. Endoplasmic reticulum stress in health and disease. Curr. Opin. Cell Biol. 18, 444-452.   DOI
17 Zhu, X., A. K. Raina, G. Perry, and M. A. Smith. 2006. Apoptosis in Alzheimer disease: a mathematical improbability. Curr. Alzheimer Res. 3, 393-396.   DOI
18 Loos, B., and A. M. Engelbrecht. 2009. Cell death: A dynamic response concept. Autophagy 5, 590-603.   DOI
19 Gjymishka, A., N. Su, and M. S. Kilberg. 2009. Transcriptional induction of the human asparagine synthetase gene during the unfolded protein response does not require the ATF6 and IRE1/XBP1 arms of the pathway. Biochem. J. 417, 695-703.   DOI
20 Broughton, B. R., D. C. Reutens, and C. G. Sobey. 2009. Apoptotic mechanisms after cerebral ischemia. Stroke 40, 331-339.   DOI   ScienceOn
21 Goldberg, M. A., S. P. Dunning, and H. F. Bunn. 1988. Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science 242, 1412-1415.   DOI
22 Gong, Y., J. Wu, Y. Huang, S. Shen, and X. Han. 2009. Nonylphenol induces apoptosis in rat testicular Sertoli cells via endoplasmic reticulum stress. Toxicol. Lett. 186, 84-95.   DOI   ScienceOn
23 Henshall, D. C. 2007. Apoptosis signalling pathways in seizure-induced neuronal death and epilepsy. Biochem. Soc. Trans. 35, 421-423.   DOI
24 Hirsch, C., R. Gauss, S. C. Horn, O. Neuber, and T. Sommer. 2009. The ubiquitylation machinery of the endoplasmic reticulum. Nature 458, 453-460.   DOI
25 Kim, I., W. Xu, and J. C. Reed. 2008. Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat. Rev. Drug. Discov. 7, 1013-1030.   DOI
26 Kim, S. W., S. P. Chung, S. H. Kim, J. S. Choi, K. Kwon, and O. Y. Kwon. 2007. Ischemia-responsive protein (irp94) gene expression in neurons. Z. Naturforsch [C] 62, 592-596.
27 Lai, E., T. Teodoro, and A. Volchuk. 2007. Endoplasmic reticulum stress: signaling the unfolded protein response. Physiology (Bethesda) 22, 193-201.   DOI   ScienceOn