Oxidative stress and cell proliferation

Cotgreave IA, Gerdes RG. 1998. Recent trends in glutathione biochemistry— glutathione-protein interactions A molecular link between oxidative stress and cell proliferation Biochem Biophys Res Commun 242 1-9. 

Zhaorigetu, S., Sasaki, M., Watanabe, H., and Kato, N. "Supplemental silk protein, sericin, suppresses colon tumorigenesis in 1,2-dimethylhydrazine-treated mice by reducing oxidative stress and cell proliferation". Biosci. Biotechnol. Biochem. 65(10), 2181-2186 (2001). 

Oxidative stress and cell proliferation 3.1. Oxygen toxicity... 

Regarding cancer, potential mechanisms include genotoxicity, altered DNA methyla-tion, oxidative stress, altered cell proliferation, cocarcinogenesis, and tumor promotion. ... 

PPARa may also have a role in controlling apoptosis, cell proliferation, inflammation, and oxidative stress. Thus, peroxisomal proliferators also stimulate DNA synthesis, liver growth, and inhibit apoptosis. 

The evidence for DNA damage in peroxisomal proliferator-treated animals is more equivocal with some studies, reporting no change in markers such as 8-hydroxydeoxyguanosine residues, whereas other studies indicate otherwise. Also, increased expression of DNA repair enzymes has been reported. The relationship between oxidative stress and signaling for cell proliferation however is not clear. 

Refractory species such as guinea pig seem to have fewer PPARa receptors in the liver, and observations suggest there are significant differences between rodents and humans in a number of aspects of the response. Recent studies in cynomologous monkeys treated with ciprofibrate have detected peroxisomal proliferation but only found slight changes in certain parameters [e.g., messenger RNA (mRNA) induction for acyl CoA oxidase] of minimal oxidative stress, and despite hypertrophy, cell proliferation was not detected. 

Burdon, R.H., Gill, V. Rice-Evans, C. (1990) Oxidative stress and tumour cell proliferation. Free Rad. Res. Commun., 11, 65-76... 

PPAR a receptor, gap junctional intercellular communication, and replicative DNA synthesis (Isenberg et al. 2000, 2001 Smith et al. 2000). Two major mechanisms have been proposed to account for peroxisome proliferator-induced hepatocarcinogenicity in rodents induction of sustained oxidative stress and enhanced cell proliferation and promotion. Suppression of hepatocellular apoptosis has also been suggested to play a role. 

Kinoshita, A., Wanibuchi, H., Wei, M., Yunokl, T., Fukushima, S. (2007). Elevation of 8-hydroxydeoxyguanosine and cell proliferation via generation of oxidative stress by organic arsenicals contributes to their carcinogenicity in the rat liver and bladder. Toxicol. Appl. Pharmacol. 221 295-305. 

In vitro and animal studies clearly point to a central role of several distinct but interconnected redox-sensitive pathways in the pathogenesis of inflammation [47]. It has been hypothesized that oxidative stress occurs as a result of the depletion of the cellular content of reduced glutathione. A sublethal oxidative stress can activate redox-sensitive kinase cascades and transcription factors, NF-kB and AP-1, with resulting increases in the expression of factors associated with an inflammatory response and cellular proliferation. Evidence has been collected suggesting that oxidative stress and the ensuing modification of the cellular redox status may be associated with the induction of cell death either via stimulation of apoptosis and/or necrosis. It is well known that cell death is a common feature of the inflammatory process [48]. 

---