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Endoplasmic reticulum (ER) stress and major chemotherapeutic agents damage DNA by generating reactive oxygen species (ROS). Here we show that ER stress and chemotherapy induce leukotriene C4 (LTC4) biosynthesis by transcriptionally upregulating and activating the enzyme microsomal glutathione-S-transferase 2 (MGST2) in cells of non-haematopoietic lineage. ER stress and chemotherapy also trigger nuclear translocation of the two LTC4 receptors. Acting in an intracrine manner, LTC4 then elicits nuclear translocation of NADPH oxidase 4 (NOX4), ROS accumulation and oxidative DNA damage. Mgst2 deficiency, RNAi and LTC4 receptor antagonists abolish ER stress- and chemotherapy-induced ROS and oxidative DNA damage in vitro and in mouse kidneys. Cell death and mouse morbidity are also significantly attenuated. Hence, MGST2-generated LTC4 is a major mediator of ER stress- and chemotherapy-triggered oxidative stress and oxidative DNA damage. LTC4 inhibitors, commonly used for asthma, could find broad clinical use in major human pathologies associated with ER stress-activated NOX4.
Pubmed ID: 26656251
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Light cycler software for analysis of quatitative real time PCR
View all literature mentionsA software for primer design. The user can choose the target sequence or gene and design primers for the real-time PCR. After, the user can examine the results and choose from the recommended probes.
View all literature mentionsData analysis, graphing, and management application that allows users to import, manipulate, analyze data, and create customized plots. Plots include x-y probability, histogram, box, percentile, horizontal bar, stack bar, column, stack column, polar, and pie. Binned data can be exported to a histogram, step plot, or spike plot. KaleidaGraph works with Windows and Macintosh systems.
View all literature mentionsStrain Type: Not Specified This is a legacy resource.
View all literature mentionslaboratory mouse with name 129/Sv from MGI.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionslaboratory mouse with name 129/Sv from MGI.
View all literature mentionsCell line U266B1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HaCaT is a Spontaneously immortalized cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line B16-F10 is a Cancer cell line with a species of origin Mus musculus (Mouse)
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