Tumor Necrosis Factor-α Generates Reactive Oxygen Species via a Cytosolic Phospholipase A2-linked Cascade

Woo, Chang Hoon; Eom, Young Woo; Yoo, Min; You, Hae Jin; Han, Ho Jae; Song, Woo Keun; Yoo, Yung Joon; Chun, Jaesun; Kim, Jae Hong

doi:10.1074/jbc.m005638200

Cited by 220 publications

(178 citation statements)

References 31 publications

Supporting

Mentioning

166

Contrasting

Order By: Relevance

“…In fact under physiological conditions, the transient generation of ROS, within boundaries, appears to be essential to maintain cellular homeostasis. ROS as messengers have been associated to signaling by insulin, cytokines and many growth factors [35,36], whose activity regulates classic signaling cascades such as the extracellular ERK, JNK, and MAPK cascades, as well as the PI3-K/Akt, PLC-γ1 and JAK/STAT pathways [37,38]. These pathways in turn exert their phenotypic effects largely by modulating the activities of central transcription factors, among them NF-kB, AP-1, Nrf2, FoxOs, HIF-1α and p53 [39,40].…”

Section: The Role Of Ros In Signal Transductionmentioning

confidence: 99%

Taking a “good” look at free radicals in the aging process

Hekimi

Lapointe

Yang

2011

Trends in Cell Biology

503

371

View full text Add to dashboard Cite

The mitochondrial free radical theory of aging (MFRTA) proposes that aging is caused by damage to macromolecules from mitochondrial reactive oxygen species (ROS). This is based on the observed association of the rate of aging and the aged phenotype with the generation of ROS and with oxidative damage. The theory has led to the strong conviction in the general public that the consumption of antioxidants is crucial to health and beneficial to lifespan. However, a variety of recent findings convincingly demonstrate that ROS generation and oxidative damage cannot be the cause of aging. Here we propose that ROS play a role in mediating a stress response to agedependent damage, which could generate the observed correlation between aging and ROS without implying that ROS cause aging. Redefining our understanding of the relationship between ROS and agingMitochondria are a major source of reactive oxygen species (ROS), a type of molecule that includes free radicals such as superoxide. ROS spontaneously oxidize and damage macromolecules such as proteins, lipids and nucleic acids. Cells and organisms are said to be sustaining oxidative stress when an imbalance between ROS generation and detoxification or repair leads to an increase in the level of ROS-dependent damage. The mitochondrial free radical theory of aging (MFRTA) has provided an attractive framework that integrates numerous observations about the generation, the toxicity and the detoxification of ROS, as well as about how these parameters change with the physiological state of cells and organisms and with chronological age. The theory proposes that aging is actually caused by the toxicity of ROS through a vicious cycle in which ROS damage to the constituents of mitochondria leads to the generation of more ROS. The theory is based on numerous observations, including (1) that there is a strong correlation between chronological age and the level of ROS generation and oxidative damage, (2) that mitochondrial function is gradually lost during aging, (3) that inhibition of mitochondrial function can enhance ROS production, and (4) that several age-dependent diseases are associated with severe increases in oxidative stress.The strength of the MFRTA is that it provides a framework for many observations while also stating a plausible causal theory of aging. Furthermore, it provided a clear research program by proposing a theory to be tested as well as by suggesting that decreasing the generation of ROS will result in health benefits. In fact the MFRTA is often taught in textbooks and in *

show abstract

Section: The Role Of Ros In Signal Transductionmentioning

confidence: 99%

Taking a “good” look at free radicals in the aging process

Hekimi

Lapointe

Yang

2011

Trends in Cell Biology

503

371

View full text Add to dashboard Cite

show abstract

“…While ROS generation is not believed to be important in TNF-mediated apoptosis, generation of ROS by TNFα is critical for the phagocytic immune response against invading pathogens. (Woo et al, 2000).…”

Section: Receptorsmentioning

confidence: 99%

Regulation and measurement of oxidative stress in apoptosis

Curtin

Donovan

Cotter

2002

Journal of Immunological Methods

511

350

View full text Add to dashboard Cite

“…3,4 On the other hand, hepatocyte apoptosis and liver injury could be also caused by Fas activation induced by Fas ligand-bearing T cells or agonistic antibodies. 2,3 Although multiple death mechanisms can be activated by the death receptors, generation of reactive oxygen species (ROS) is a critical one, [5][6][7][8][9][10][11][12][13] and antioxidants have been shown to alleviate cell death induced by TNF-␣ 9,14 or Fas 7,15 activation. Despite the importance of ROS, the mechanisms of their generation remain controversial and unresolved.…”

mentioning

confidence: 99%

Bid-dependent generation of oxygen radicals promotes death receptor activation-induced apoptosis in murine hepatocytes

et al. 2004

View full text Add to dashboard Cite

Activation of tumor necrosis factor receptor 1 or Fas leads to the generation of reactive oxygen species, which are important to the cytotoxic effects of tumor necrosis factor ␣ (TNF-␣) or Fas ligand. However, how these radicals are generated following receptor ligation is not clear. Using primary hepatocytes, we found that TNF-␣ or anti-Fas antibodyinduced burst of oxygen radicals was mainly derived from the mitochondria. We discovered that Bid-a pro-death Bcl-2 family protein activated by ligated death receptors-was the main intracellular molecule signaling the generation of the radicals by targeting to the mitochondria and that the majority of oxygen radical production was dependent on Bid. Reactive oxygen species contributed to cell death and caspase activation by promoting FLICE-inhibitory protein degradation and mitochondrial release of cytochrome c. For the latter part, the oxygen radicals did not affect Bak oligomerization but instead promoted mitochondrial cristae reorganization and membrane lipid peroxidation. Antioxidants could reverse these changes and therefore protect against TNF-␣ or anti-Fas-induced apoptosis. In conclusion, our studies established the signaling pathway from death receptor engagement to oxygen radical generation and determined the mechanism by which reactive oxygen species contributed to hepatocyte apoptosis following death receptor activation. (HEPATOLOGY 2004;40:403-413.)

show abstract

Tumor Necrosis Factor-α Generates Reactive Oxygen Species via a Cytosolic Phospholipase A2-linked Cascade

Cited by 220 publications

References 31 publications

Taking a “good” look at free radicals in the aging process

Taking a “good” look at free radicals in the aging process

Regulation and measurement of oxidative stress in apoptosis

Bid-dependent generation of oxygen radicals promotes death receptor activation-induced apoptosis in murine hepatocytes

Contact Info

Product

Resources

About