Hanyang Med Rev.  2013 May;33(2):77-82. 10.7599/hmr.2013.33.2.77.

Role of Reactive Oxygen Species in Cell Death Pathways

Affiliations
  • 1Department of Life Science, Ewha Womans University, Seoul, Korea. kangsw@ewha.ac.kr

Abstract

Reactive oxygen species (ROS) are the chemical species that includes the superoxide anion, hydrogen peroxide and hydrogen radical. These ROS are simply thought as a group of molecules harmful to cells because they oxidize proteins, lipids and DNA, and they mediate cell death including apoptosis or necrosis. On the other hand, ROS have been shown to act as essential intracellular second messengers for certain cytokines and growth factors. Although the importance of ROS in the execution of cell death is controversial, ROS are likely to be involved in the signal transduction mechanism for cell death as signaling intermediates in death receptor initiated signaling pathways, specifically in the tumor necrosis factor alpha-tumor necrosis factor receptor 1 (TNFalpha-TNFR1) pathway. In this review, using TNFalpha-TNFR as the model system, we attempt to address the involvement of intracellular ROS in TNFalpha induced cell death, including apoptosis, necrosis and an alternative form of programmed cell death, necroptosis.

Keyword

Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Apoptosis; Necrosis

MeSH Terms

Apoptosis
Cell Death
Cytokines
DNA
Hand
Hydrogen
Hydrogen Peroxide
Intercellular Signaling Peptides and Proteins
Necrosis
Proteins
Reactive Oxygen Species
Second Messenger Systems
Signal Transduction
Superoxides
Tumor Necrosis Factor-alpha
Cytokines
DNA
Hydrogen
Hydrogen Peroxide
Intercellular Signaling Peptides and Proteins
Proteins
Reactive Oxygen Species
Superoxides
Tumor Necrosis Factor-alpha

Figure

  • Fig. 1 TNFα induced formation of apoptotic and necroptotic signaling complexes. TNFR1, tumor necrosis factor receptor 1; TRADD, TNFR type 1-associated death domain protein; TRAF2, TNF receptor-associated factor 2; cIAP1, cellular inhibitor of apoptosis 1; JNK, c-Jun N-terminal kinase; RIP1, receptor-interacting protein 1; FADD, Fas-associated death domain; GSH, glutathione; MnSOD, manganese-dependent superoxide dismutase; PRx, peroxiredoxin-3; NF-κB, nuclear factor kappa-light-chain-enhancer of activator B cells; ROS, reactive oxygen species.


Cited by  3 articles

Do Reactive Oxygen Species Cause Aging?
Seong Eon Ryu
Hanyang Med Rev. 2013;33(2):75-76.    doi: 10.7599/hmr.2013.33.2.75.

Effect of apoptosis on G361 cells by Cimicifuga rhizoma extract
Byul Bo Ra Choi, Gyoo Cheon Kim, Jin Woo Hong, Sang Rye Park
J Korean Acad Oral Health. 2019;43(2):72-77.    doi: 10.11149/jkaoh.2019.43.2.72.

Neuroprotective effects of Momordica charantia extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SK-N-MC cells
Kkot Byeol Kim, Seonah Lee, Jae Hyeok Heo, Jung hee Kim
J Nutr Health. 2017;50(5):415-425.    doi: 10.4163/jnh.2017.50.5.415.


Reference

1. Rhee SG. Cell signaling. H2O2, a necessary evil for cell signaling. Science. 2006; 312:1882–1883.
2. Rhee SG, Bae YS, Lee SR, Kwon J. Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci STKE. 2000; 2000:pe1.
Article
3. Ozben T. Oxidative stress and apoptosis: impact on cancer therapy. J Pharm Sci. 2007; 96:2181–2196.
Article
4. Rhee SG, Kang SW, Jeong W, Chang TS, Yang KS, Woo HA. Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins. Curr Opin Cell Biol. 2005; 17:183–189.
Article
5. Rhee SG, Chang TS, Bae YS, Lee SR, Kang SW. Cellular regulation by hydrogen peroxide. J Am Soc Nephrol. 2003; 14:S211–S215.
Article
6. Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999; 15:269–290.
Article
7. Chandra J, Samali A, Orrenius S. Triggering and modulation of apoptosis by oxidative stress. Free Radic Biol Med. 2000; 29:323–333.
Article
8. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003; 10:45–65.
Article
9. Ding WX, Ni HM, DiFrancesca D, Stolz DB, Yin XM. Bid-dependent generation of oxygen radicals promotes death receptor activation-induced apoptosis in murine hepatocytes. Hepatology. 2004; 40:403–413.
Article
10. Sakon S, Xue X, Takekawa M, Sasazuki T, Okazaki T, Kojima Y, et al. NF-kappaB inhibits TNF-induced accumulation of ROS that mediate prolonged MAPK activation and necrotic cell death. EMBO J. 2003; 22:3898–3909.
Article
11. Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell. 2005; 120:649–661.
Article
12. Sullivan DM, Wehr NB, Fergusson MM, Levine RL, Finkel T. Identification of oxidant-sensitive proteins: TNF-alpha induces protein glutathiolation. Biochemistry. 2000; 39:11121–11128.
Article
13. Han D, Hanawa N, Saberi B, Kaplowitz N. Mechanisms of liver injury. III. Role of glutathione redox status in liver injury. Am J Physiol Gastrointest Liver Physiol. 2006; 291:G1–G7.
Article
14. Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001; 30:1191–1212.
Article
15. Hanawa N, Shinohara M, Saberi B, Gaarde WA, Han D, Kaplowitz N. Role of JNK translocation to mitochondria leading to inhibition of mitochondria bioenergetics in acetaminophen-induced liver injury. J Biol Chem. 2008; 283:13565–13577.
Article
16. Liu H, Lo CR, Czaja MJ. NF-kappaB inhibition sensitizes hepatocytes to TNF-induced apoptosis through a sustained activation of JNK and c-Jun. Hepatology. 2002; 35:772–778.
Article
17. Zhou Q, Lam PY, Han D, Cadenas E. c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons. J Neurochem. 2008; 104:325–335.
Article
18. Liu Y, Min W. Thioredoxin promotes ASK1 ubiquitination and degradation to inhibit ASK1-mediated apoptosis in a redox activity-independent manner. Circ Res. 2002; 90:1259–1266.
Article
19. Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, et al. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 1998; 17:2596–2606.
Article
20. Hochedlinger K, Wagner EF, Sabapathy K. Differential effects of JNK1 and JNK2 on signal specific induction of apoptosis. Oncogene. 2002; 21:2441–2445.
Article
21. Das M, Sabio G, Jiang F, Rincon M, Flavell RA, Davis RJ. Induction of hepatitis by JNK-mediated expression of TNF-alpha. Cell. 2009; 136:249–260.
Article
22. Han D, Canali R, Rettori D, Kaplowitz N. Effect of glutathione depletion on sites and topology of superoxide and hydrogen peroxide production in mitochondria. Mol Pharmacol. 2003; 64:1136–1144.
Article
23. De Vos K, Goossens V, Boone E, Vercammen D, Vancompernolle K, Vandenabeele P, et al. The 55-kDa tumor necrosis factor receptor induces clustering of mitochondria through its membrane-proximal region. J Biol Chem. 1998; 273:9673–9680.
Article
24. Thomas WD, Zhang XD, Franco AV, Nguyen T, Hersey P. TNF-related apoptosis-inducing ligand-induced apoptosis of melanoma is associated with changes in mitochondrial membrane potential and perinuclear clustering of mitochondria. J Immunol. 2000; 165:5612–5620.
Article
25. Boldin MP, Goncharov TM, Goltsev YV, Wallach D. Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1-and TNF receptor-induced cell death. Cell. 1996; 85:803–815.
Article
26. Tait SW, Green DR. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 2010; 11:621–632.
Article
27. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, et al. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997; 91:479–489.
Article
28. Srinivasula SM, Hegde R, Saleh A, Datta P, Shiozaki E, Chai J, et al. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature. 2001; 410:112–116.
Article
29. Tyurina YY, Tyurin VA, Carta G, Quinn PJ, Schor NF, Kagan VE. Direct evidence for antioxidant effect of Bcl-2 in PC12 rat pheochromocytoma cells. Arch Biochem Biophys. 1997; 344:413–423.
Article
30. Fiers W, Beyaert R, Declercq W, Vandenabeele P. More than one way to die: apoptosis, necrosis and reactive oxygen damage. Oncogene. 1999; 18:7719–7730.
Article
31. Vercammen D, Beyaert R, Denecker G, Goossens V, Van Loo G, Declercq W, et al. Inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor. J Exp Med. 1998; 187:1477–1485.
Article
32. Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, et al. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000; 1:489–495.
Article
33. Kawahara A, Ohsawa Y, Matsumura H, Uchiyama Y, Nagata S. Caspase-independent cell killing by Fas-associated protein with death domain. J Cell Biol. 1998; 143:1353–1360.
Article
34. Lin Y, Choksi S, Shen HM, Yang QF, Hur GM, Kim YS, et al. Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation. J Biol Chem. 2004; 279:10822–10828.
Article
35. Leist M, Jaattela M. Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol. 2001; 2:589–598.
Article
36. Matthews N, Neale ML, Jackson SK, Stark JM. Tumour cell killing by tumour necrosis factor: inhibition by anaerobic conditions, free-radical scavengers and inhibitors of arachidonate metabolism. Immunology. 1987; 62:153–155.
37. Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, Beyaert R, Jacob WA, Fiers W. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem. 1992; 267:5317–5323.
Article
38. Meylan E, Tschopp J. The RIP kinases: crucial integrators of cellular stress. Trends Biochem Sci. 2005; 30:151–159.
Article
39. Chan FK, Shisler J, Bixby JG, Felices M, Zheng L, Appel M, et al. A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses. J Biol Chem. 2003; 278:51613–51621.
Article
40. Lin Y, Devin A, Rodriguez Y, Liu ZG. Cleavage of the death domain kinase RIP by caspase-8 prompts TNF-induced apoptosis. Genes Dev. 1999; 13:2514–2526.
Article
41. Shen HM, Lin Y, Choksi S, Tran J, Jin T, Chang L, et al. Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death. Mol Cell Biol. 2004; 24:5914–5922.
Article
42. Kim YS, Morgan MJ, Choksi S, Liu ZG. TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. Mol Cell. 2007; 26:675–687.
Article
43. Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, et al. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009; 137:1112–1123.
Article
44. He S, Wang L, Miao L, Wang T, Du F, Zhao L, et al. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009; 137:1100–1111.
Article
45. Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, et al. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science. 2009; 325:332–336.
Article
46. Wang L, Du F, Wang X. TNF-alpha induces two distinct caspase-8 activation pathways. Cell. 2008; 133:693–703.
Article
47. Nicotera P, Melino G. Regulation of the apoptosis-necrosis switch. Oncogene. 2004; 23:2757–2765.
Article
48. Sun L, Wang H, Wang Z, He S, Chen S, Liao D, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012; 148:213–227.
Article
49. Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012; 148:228–243.
Article
50. Yazdanpanah B, Wiegmann K, Tchikov V, Krut O, Pongratz C, Schramm M, et al. Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. Nature. 2009; 460:1159–1163.
Article
Full Text Links
  • HMR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr