Browse > Article

Involvement of Caspases and Bcl-2 Family in Nitric Oxide-Induced Apoptosis of Rat PC12 Cells  

Jeong, Yeon-Jin (Dental Science Research Institute, 2nd Stage of Brain Korea 21, School of Dentistry, Chonnam National University)
Jung, Ji-Yeon (Dental Science Research Institute, 2nd Stage of Brain Korea 21, School of Dentistry, Chonnam National University)
Lee, Jin-Ha (Dental Science Research Institute, 2nd Stage of Brain Korea 21, School of Dentistry, Chonnam National University)
Cho, Jin-Hyoung (Dental Science Research Institute, 2nd Stage of Brain Korea 21, School of Dentistry, Chonnam National University)
Lee, Guem-Sug (Dental Science Research Institute, 2nd Stage of Brain Korea 21, School of Dentistry, Chonnam National University)
Kim, Sun-Hun (Dental Science Research Institute, 2nd Stage of Brain Korea 21, School of Dentistry, Chonnam National University)
Kim, Won-Jae (Dental Science Research Institute, 2nd Stage of Brain Korea 21, School of Dentistry, Chonnam National University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.10, no.6, 2006 , pp. 329-335 More about this Journal
Abstract
This study was aimed to investigate the nitric oxide (NO)-induced cytotoxic mechanism in PC12 cells. Sodium nitroprusside (SNP), an NO donor, decreased the viability of PC12 cells in dose-and time-dependent manners. SNP enhanced the production of reactive oxygen species (ROS), and gave rise to apoptotic morphological changes including cell shrinkage, chromatin condensation, and DNA fragmentation. Expression of Bax was not affected, whereas Bcl-2 was downregulated in SNP-treated PC12 cells. SNP augmented the release of cytochrome c from mitochondria into cytosol and enhanced caspase -8, -9, and -3 activities. SNP upregulated both Fas and Fas-L, which are known to be components of death receptor assembly. These results suggest that NO induces apoptosis of PC12 cells through both mitochondria-and death receptor-mediated pathways mediated by ROS and Bcl-2 family.
Keywords
Apoptosis; Nitric oxide; PC12 cells; Bcl-2 family; Caspase;
Citations & Related Records

Times Cited By SCOPUS : 0
연도 인용수 순위
  • Reference
1 Beer R, Frenz G, Schopf M, Reindl M, Zelger B, Schmutzhard E, Poewe W, Kampfl A. Expression of Fas and Fas ligand after experimental traumatic brain injury in the rat. J Cereb Blood Flow Metab 20: 669-677, 2000   DOI
2 Bolanos JP, Almeida A, Stewart V, Penchen S, Land JM, Clark JB, Heals SJR. Nitric oxide-mediated mitochondrial damage in the brain: mechanisms and implications for neurodegenerative diseases. J Neurochem 68: 2227-2240, 1997   DOI   ScienceOn
3 Brown GC. Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411: 351-369, 1999   DOI   ScienceOn
4 Crompton M. Mitochondrial intermembrane junctional complexes and their role in cell death. J Physiol 529: 11-21, 2000   DOI   ScienceOn
5 Fleury C, Miqnotte B, Vayssiere JL. Mitochondrial reactive oxygen species in cell death signaling. Biochimie 84: 131-141, 2002   DOI   ScienceOn
6 Fraker PJ, King LE, Lill-Elghanian D, Telford WG. Quantification of apoptotic events in pure and heterogeneous populations of cells using the flow cytometer. Methods Cell Biol 46: 57-76, 1995   DOI
7 Lee SJ, Kim WL, Kang HS, Lee CK, Lee BJ, Kang KM, Kang SG. Studies on the regulation of ovarian granulosa cell apotosis by gonadotropins and nitric oxide. Dev Reprod 2: 157-164, 1997
8 Leist M, Single B, Naumann H, Fava E, Simon B, Kuhnle S, Nicotera P. Nitric oxide inhibits execution of apoptosis at two distinct ATP-dependent steps upstream and downstream of mitochondrial cytochrome c release. Biochem Biophys Res Commun 258: 215-221, 1999   DOI   ScienceOn
9 Peuchen S, Bolanos JP, Heales SJ, Almeida A, Duchen MR, Clark JB. Interrelationships between astrocyte function, oxidative stress and antioxident status within the central nervous system. Prog Neurobiol 52: 261-281, 1997   DOI   ScienceOn
10 Roth JA, Feng L, Walowitz J, Browne RW. Manganese -induced rat pheochromocytoma (PC12) cell death is independent of caspase activation. J Neurosci Res 61: 162-171, 2000   DOI   ScienceOn
11 Tsujimoto Y, Shimizu S. Bcl-2 family: life-or-death switch. FEBS Lett 466: 6-10, 2000   DOI   ScienceOn
12 Yuyama K, Yamamoto H, Nishozaki I, Kato T, Sora I, Yamamoto T. Caspase-independent cell death by low concentrations of nitric oxide in PC12 cells: Involvement of cytochrome c oxidase inhibition and the production of reactive oxygen species in mitochondria. J Neurosci Res 73: 351-363, 2003   DOI   ScienceOn
13 Herrera B, Alvarez AM, Sanchez A, Fernandez M, Roncero C, Benito M, Fabregat I. Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor (beta) in fetal hepatocytes. FASEB J 15: 741-751, 2001   DOI   ScienceOn
14 Eastman A. Assays for DNA fragmentation, endonucleases, and intracellular pH and $Ca^{2+}$ associated with apoptosis. Methods Cell Biol 46: 41-55, 1995   DOI
15 Krajewski S, Krajewska M, Ellerby LM, welsh K, Xie Z, Deveraux QL. Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia. Proc Natl Acad Sci USA 96: 5752-5759, 1999
16 Ankarcrona M, Dypbukt JM, Bonfoco E, Zhivotovsky B, Orrenius S, Lipton SA, Nicotera P. Glutamate-induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 15: 961-973, 1995   DOI   ScienceOn
17 Cheng EH, Nicholas J, Bellows DS, Hayward GS, Guo HG, Reitz MS, Hardwick JM. A Bcl-2 homolog encoded by kaposi sarcoma- associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak. Proc Natl Acad Sci USA 94: 690-694, 1997
18 Bal-Price A, Brown GC. Nitric-Oxide-Induced Necrosis and Apoptosis in PC12 cells mediated by mitochondria. J Neurochem 75: 1455-1464, 2000   DOI   ScienceOn
19 Dawson VL, Dawson TM. Nitric oxide neurotoxicity. J Chem Neuroanat 10: 179-190, 1996   DOI   ScienceOn
20 Gottlieb E, Vander Heiden MG, Thompson CB. Bcl-xl prevents the initial decrease in mitochondrial membrane potential and subsequent reactive oxygen species production during tumor necrosis factor alpha-induced apoptosis. Mol Cell Biol 20: 5680-5689, 2000   DOI   ScienceOn
21 Earnshaw WC, Marins LM, Kaufmann SH. Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu. Rev Biochem 68: 383-424, 1999   DOI   ScienceOn
22 Howard S, Bottino C, Brooke S, Cheng E, Giffard RG, Sapolsky R. Neuroprotective effects of Bcl-2 overexpression in hippocampal cultures: interactions with pathways of oxidative damage. J Neurochem 83: 914-923, 2002   DOI   ScienceOn
23 Gross SS, Wolin MS. Nitric oxide: pathophysiological mechanisms. Annu Rev Physiol 57: 737-769, 1995   DOI   ScienceOn
24 Hemish J, Nakaya N, Mittal V, Enikolopov G. Nitric oxide activates diverse signaling pathways to regulate gene expression. J Biol Chem 278: 42321-42329, 2003   DOI   ScienceOn
25 Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science 281: 1322-1326, 1998   DOI   ScienceOn
26 Huerta-Yepez S, Vega M, Jazirehi A, Garban H, Hongo F, Cheng G, Bonavida B. Nitric oxide sensitizes prostate carcinoma cell lines to TRAIL-mediated apoptosis via inactivation of NF-${\kappa}B$ and inhibition of Bcl-XL expression. Oncogene 23: 4993-5003, 2004   DOI   ScienceOn
27 Facchinetti F, Furegato S, Terrazzino S, Leon A. $H_2O_2$ induces upregulation of Fas and Fas ligand expression in NGF-differentiated HGF cells: modulation by cAMP. J Neurosci Res 69: 178-188, 2002   DOI   ScienceOn
28 Jenner P, Olanow CW. Oxidative stress and pathogenesis of Parkinson's disease. Neurology 47: S161-S170, 1996   DOI   ScienceOn
29 Starkov AA, Polster BM, Fiskum G. Regulation of hydrogen peroxide production by brain mitochondria by calcium and Bax. J Neurochem 83: 220-228, 2002   DOI   ScienceOn
30 Murphy MP. Nitric oxide and cell death. Biochem Biophys Acta 1411: 401-414, 1999   DOI   ScienceOn