TY - JOUR A1 - Münch, Miriam A1 - Hsin, Chih-Hsuan A1 - Ferber, Elena A1 - Berger, Susanne A1 - Müller, Martin J. T1 - Reactive electrophilic oxylipins trigger a heat stress-like response through HSFA1 transcription factors JF - Journal of Experimental Botany N2 - Electrophilic oxylipins trigger a heat-shock-like response in the absence of heat through the canonical heat-shock transcription factor A1, thereby helping to cope with stresses associated with protein damage.Abiotic and biotic stresses are often characterized by an induction of reactive electrophile species (RES) such as the jasmonate 12-oxo-phytodienoic acid (OPDA) or the structurally related phytoprostanes. Previously, RES oxylipins have been shown massively to induce heat-shock-response (HSR) genes including HSP101 chaperones. Moreover, jasmonates have been reported to play a role in basal thermotolerance. We show that representative HSR marker genes are strongly induced by RES oxylipins through the four master regulator transcription factors HSFA1a, b, d, and e essential for short-term adaptation to heat stress in Arabidopsis. When compared with Arabidopsis seedlings treated at the optimal acclimation temperature of 37 A degrees C, the exogenous application of RES oxylipins at 20 A degrees C induced a much weaker induction of HSP101 at both the gene and protein expression levels which, however, was not sufficient to confer short-term acquired thermotolerance. Moreover, jasmonate-deficient mutant lines displayed a wild-type-like HSR and were not compromised in acquiring thermotolerance. Hence, the OPDA- and RES oxylipin-induced HSR is not sufficient to protect seedlings from severe heat stress but may help plants to cope better with stresses associated with protein unfolding by inducing a battery of chaperones in the absence of heat. KW - arabidopsis-thaliana KW - shock response KW - gene-expression KW - model KW - acquired thermotolerance KW - 12-oxo-phytodienoic acid KW - thermotolerance KW - plants KW - detoxification KW - acquisition KW - activation KW - heat stress KW - jasmonates KW - phytoprostanes KW - reactive electrophilic species KW - unfolded protein response Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186766 VL - 67 IS - 21 ER - TY - JOUR A1 - Cardani, Diego A1 - Sardi, Claudia A1 - La Ferla, Barbara A1 - D'Orazio, Guiseppe A1 - Sommariva, Michele A1 - Marcucci, Fabrizio A1 - Olivero, Daniela A1 - Tagliabue, Elda A1 - Koepsell, Hermann A1 - Nicotra, Francesco A1 - Balsari, Andrea A1 - Rumio, Christiano T1 - Sodium glucose cotransporter 1 ligand BLF501 as a novel tool for management of gastrointestinal mucositis JF - Molecular Cancer N2 - Background: Recent studies demonstrated that engagement of sodium glucose transporter 1 (SGLT-1) by orally administered D-glucose protects the intestinal mucosa from lipopolysaccharide (LPS)-induced injury. We tested whether SGLT-1 engagement might protect the intestinal mucosa from doxorubicin (DXR)- and 5-fluorouracil (5-FU)-induced injury in animal models mimicking acute or chronic mucositis. Methods: Mice were treated intraperitoneally with DXR, alone or in combination with 5-FU, and orally with BLF501, a glucose-derived synthetic compound with high affinity for SGLT-1. Intestinal mucosal epithelium integrity was assessed by histological analysis, cellular proliferation assays, real-time PCR gene expression assays and Western blot assays. Student's t-test (paired two-tailed) and X-2 analyses were used for comparisons between groups. Differences were considered significant at p < 0.05. Results: BLF501 administration in mice treated with DXR and/or 5-FU decreased the injuries to the mucosa in terms of epithelial integrity and cellular proliferative ability. Co-treatment with BLF501 led to a normal expression and distribution of both zonula occludens-1 (ZO-1) and beta-catenin, which were underexpressed after treatment with either chemotherapeutic agent alone. BLF501 administration also restored normal expression of caspase-3 and ezrin/radixin/moesin (ERM), which were overexpressed after treatment with DXR and 5-FU. In SGLT1-/- mice, BLF501 had no detectable effects. BLF501 administration in wild-type mice with growing A431 tumors did not modify antitumor activity of DXR. Conclusions: BLF501-induced protection of the intestinal mucosa is a promising novel therapeutic approach to reducing the severity of chemotherapy-induced mucositis. KW - apoptosis KW - prevention KW - doxorubicin KW - cancer KW - gastrointestinal mucositis KW - SGLT-1 KW - synthetic D-glucose analogy KW - chemotherapy KW - inflammation KW - clinical practice guidelines KW - intestinal mucositis KW - epithelial cells KW - oral mucositis KW - gene-expression Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117352 SN - 1476-4598 VL - 13 IS - 23 ER -