The level of intracellular glutathione is a key regulator for the induction of stress-activated signal transduction pathways including Jun N-terminal protein kinases and p38 kinase by alkylating agents - PubMed (original) (raw)
The level of intracellular glutathione is a key regulator for the induction of stress-activated signal transduction pathways including Jun N-terminal protein kinases and p38 kinase by alkylating agents
D Wilhelm et al. Mol Cell Biol. 1997 Aug.
Abstract
Monofunctional alkylating agents like methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are potent inducers of cellular stress leading to chromosomal aberrations, point mutations, and cell killing. We show that these agents induce a specific cellular stress response program which includes the activation of Jun N-terminal kinases/stress-activated protein kinases (JNK/SAPKs), p38 mitogen-activated protein kinase, and the upstream kinase SEK1/MKK4 and which depends on the reaction mechanism of the alkylating agent in question. Similar to another inducer of cellular stress, UV irradiation, damage of nuclear DNA by alkylation is not involved in the MMS-induced response. However, in contrast to UV and other inducers of the JNK/SAPKs and p38 pathways, activation of growth factor and G-protein-coupled receptors does not play a role in the MMS response. We identified the intracellular glutathione (GSH) level as critical for JNK/SAPK activation by MMS: enhancing the GSH level by pretreatment of the cells with GSH or N-acetylcysteine inhibits, whereas depletion of the cellular GSH pool causes hyperinduction of JNK/SAPK activity by MMS. In light of the JNK/SAPK-dependent induction of c-jun and c-fos transcription, and the Jun/Fos-induced transcription of xenobiotic-metabolizing enzymes, these data provide a potential critical role of JNK/SAPK and p38 in the induction of a cellular defense program against cytotoxic xenobiotics such as MMS.
Similar articles
- Induction of the SAPK activator MIG-6 by the alkylating agent methyl methanesulfonate.
van Laar T, Schouten T, van der Eb AJ, Terleth C. van Laar T, et al. Mol Carcinog. 2001 Jun;31(2):63-7. doi: 10.1002/mc.1040. Mol Carcinog. 2001. PMID: 11429782 - Differential activation of ERK, JNK/SAPK and P38/CSBP/RK map kinase family members during the cellular response to arsenite.
Liu Y, Guyton KZ, Gorospe M, Xu Q, Lee JC, Holbrook NJ. Liu Y, et al. Free Radic Biol Med. 1996;21(6):771-81. doi: 10.1016/0891-5849(96)00176-1. Free Radic Biol Med. 1996. PMID: 8902523 - Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion.
Bogoyevitch MA, Gillespie-Brown J, Ketterman AJ, Fuller SJ, Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH. Bogoyevitch MA, et al. Circ Res. 1996 Aug;79(2):162-73. doi: 10.1161/01.res.79.2.162. Circ Res. 1996. PMID: 8755992 Review. - Induction of xenobiotic enzymes by the MAP kinase pathway and the antioxidant or electrophile response element (ARE/EpRE).
Kong AN, Owuor E, Yu R, Hebbar V, Chen C, Hu R, Mandlekar S. Kong AN, et al. Drug Metab Rev. 2001 Aug-Nov;33(3-4):255-71. doi: 10.1081/dmr-120000652. Drug Metab Rev. 2001. PMID: 11768769 Review.
Cited by
- The good Samaritan glutathione-S-transferase P1: An evolving relationship in nitric oxide metabolism mediated by the direct interactions between multiple effector molecules.
Russell TM, Richardson DR. Russell TM, et al. Redox Biol. 2023 Feb;59:102568. doi: 10.1016/j.redox.2022.102568. Epub 2022 Dec 15. Redox Biol. 2023. PMID: 36563536 Free PMC article. Review. - 1,4-Benzoquinone antimicrobial agents against Staphylococcus aureus and Mycobacterium tuberculosis derived from scorpion venom.
Carcamo-Noriega EN, Sathyamoorthi S, Banerjee S, Gnanamani E, Mendoza-Trujillo M, Mata-Espinosa D, Hernández-Pando R, Veytia-Bucheli JI, Possani LD, Zare RN. Carcamo-Noriega EN, et al. Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):12642-12647. doi: 10.1073/pnas.1812334116. Epub 2019 Jun 10. Proc Natl Acad Sci U S A. 2019. PMID: 31182590 Free PMC article. - Sublinear response in lacZ mutant frequency of Muta™ Mouse spermatogonial stem cells after low dose subchronic exposure to N-ethyl-N-nitrosourea.
O'Brien JM, Walker M, Sivathayalan A, Douglas GR, Yauk CL, Marchetti F. O'Brien JM, et al. Environ Mol Mutagen. 2015 May;56(4):347-55. doi: 10.1002/em.21932. Epub 2015 Jan 17. Environ Mol Mutagen. 2015. PMID: 25598316 Free PMC article. - Ionizing radiation affects the expression of Toll-like receptors 2 and 4 in human monocytic cells through c-Jun N-terminal kinase activation.
Yoshino H, Chiba K, Saitoh T, Kashiwakura I. Yoshino H, et al. J Radiat Res. 2014 Sep;55(5):876-84. doi: 10.1093/jrr/rru040. Epub 2014 Jun 13. J Radiat Res. 2014. PMID: 24927726 Free PMC article. - Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation.
Muralidharan S, Mandrekar P. Muralidharan S, et al. J Leukoc Biol. 2013 Dec;94(6):1167-84. doi: 10.1189/jlb.0313153. Epub 2013 Aug 29. J Leukoc Biol. 2013. PMID: 23990626 Free PMC article. Review.
References
- J Biol Chem. 1995 Jun 2;270(22):12969-72 - PubMed
- Cell. 1995 Jun 30;81(7):1137-46 - PubMed
- Cell. 1995 Jun 30;81(7):1147-57 - PubMed
- Curr Opin Cell Biol. 1995 Apr;7(2):203-10 - PubMed
- Science. 1995 Jul 21;269(5222):403-7 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous