Role of glutathione in the induction of apoptosis and c-fos and c-jun mRNAs by oxidative stress in tumor cells

Tormos, Carmen; Chaves, Felipe Javier; García, María José Rodrigo; Garrido, Federico; Jover, Ramiro; O’Connor, José Enrique; Iradi, Antonio; Oltra, Ana; Oliva, Maria R.; Sáez, Guillermo T.

doi:10.1016/j.canlet.2003.11.007

Cited by 37 publications

(28 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44 DNA oxidation measurement: cell DNA was isolated and digested as described. 45 Levels of 8-oxo-2 0 -deoxyguanosine (8-oxo-dG) were measured by HPLC (Waters ODS HPLC column) followed by electrochemical and ultraviolet absorbance detection as described. 45 Cellular content of GSH and GSSG were measured by HPLC as previously described.…”

Section: Immunoprecipitation and Western-blot Analysismentioning

confidence: 99%

“…45 Levels of 8-oxo-2 0 -deoxyguanosine (8-oxo-dG) were measured by HPLC (Waters ODS HPLC column) followed by electrochemical and ultraviolet absorbance detection as described. 45 Cellular content of GSH and GSSG were measured by HPLC as previously described. 46,47 Determination of GSH in the extracellular medium…”

Section: Immunoprecipitation and Western-blot Analysismentioning

confidence: 99%

See 1 more Smart Citation

Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation

et al. 2006

Self Cite

View full text Add to dashboard Cite

Aplidins is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin s alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin s generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin s activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulation of Rac1 by transfection of small interfering RNA (siRNA) duplexes or the use of a specific Rac1 inhibitor decreased Aplidin s -induced JNK activation and cytotoxicity. Our results show that Aplidin s induces apoptosis by increasing the GSSG/GSH ratio, a necessary step for induction of oxidative stress and sustained JNK activation through Rac1 activation and MKP-1 downregulation.

show abstract

Section: Immunoprecipitation and Western-blot Analysismentioning

confidence: 99%

Section: Immunoprecipitation and Western-blot Analysismentioning

confidence: 99%

Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…Intracellular glutathione levels regulate Jun and Fos induction (Bergelson et al, 1994). Increase in the expression of cjun and cfos genes due to loss of GSH has been reported (Tormos et al, 2004). Oguro et al, (1998) also observed that GSH depletion enhanced cJun phosphorylation and AP1 binding indicating activation of this transcription factor.…”

Section: Discussionmentioning

confidence: 84%

Co-operative effect of glutathione depletion and selenium induced oxidative stress on API and NFkB expression in testicular cells in vitro: insights to regulation of spermatogenesis

Shalini

Bansal

2007

Biol. Res.

View full text Add to dashboard Cite

Previous studies have shown that transcription factors, AP1 and NFκB exert important roles in the process by which selenium regulates spermatogenesis. Glutathione, an intracellular thiol, acts as a source of reducing power and aids in maintenance of the cellular redox status. The activities of selenium are closely related to the availability of glutathione. Presently, mouse testicular cells were cultured in the presence of BSO, a known glutathione depletor, to generate oxidative stress. Selenium (Se) was added as sodium selenite to these cells at concentrations of 0.5 μM and 1.5 μM. It was observed that at 1.5 μM, Se acted as a pro-oxidant and significantly decreased the redox ratio. RT PCR analysis revealed that cjun, cfos expression increased in testicular cells cultured with Se compared to control. However, the major outcome was that the combined effect of Se supplementation and GSH depletion resulted in reduced expression of cjun and cfos while p65 expression increased. This suggests that selenium affects both these transcription factors differently. Our study indicates that though low levels of oxidative stress generated by moderate doses of selenium augments the expression of cjun and cfos, a robust increase in the ROS generation caused by the dual effect high levels of selenium and glutathione depletion leads to decrease in the expression of these genes. The present work substantiates our in vivo experiments and indicates the detrimental effect of excess selenium supplementation on male fertility.

show abstract

“…It aids in the formation of the reduced form of antioxidants like ascorbic acid and promotes detoxification of carcinogens, free radicals and xenobiotics. Rapid GSH synthesis in tumor cells is associated with high rates of cell proliferation, whilst GSH depletion is sufficient to sensitize cancer cells to the cytotoxic effects of oxidative stress and make them more vulnerable to the effects of anticancer drugs or the genes that promote apoptosis [45]. Himmetoglu et al reported significantly lower levels of glutathione peroxidase in breast cancer patients as compared to controls [46].…”

Section: Discussionmentioning

confidence: 98%

Breast cancer: Interaction between oxidant-antioxidant dynamics and inflammation in Indian females

et al. 2009

View full text Add to dashboard Cite

show abstract

Role of glutathione in the induction of apoptosis and c-fos and c-jun mRNAs by oxidative stress in tumor cells

Cited by 37 publications

References 32 publications

Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation

Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 phosphatase downregulation

Co-operative effect of glutathione depletion and selenium induced oxidative stress on API and NFkB expression in testicular cells in vitro: insights to regulation of spermatogenesis

Breast cancer: Interaction between oxidant-antioxidant dynamics and inflammation in Indian females

Contact Info

Product

Resources

About