Kaufmann, Kai B. and Al-Rifai, Nafisah and Ulbrich, Felix and Schallner, Nils and Ruecker, Hannelore and Enzinger, Monika and Petkes, Hermina and Pitzl, Sebastian and Goebel, Ulrich and Amslinger, Sabine (2015) The Cytoprotective Effects of E-alpha- (4-Methoxyphenyl)-2 ',3,4,4 '-Tetramethoxychalcone (E-alpha-p-OMe-C6H4-TMC)-A Novel and Non-Cytotoxic HO-1 Inducer. PLOS ONE, 10 (11): e0142932. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Cell protection against different noxious stimuli like oxidative stress or chemical toxins plays a central role in the treatment of many diseases. The inducible heme oxygenase isoform, heme oxygenase-1 (HO-1), is known to protect cells against a variety of harmful conditions including apoptosis. Because a number of medium strong electrophiles from a series of alpha-X-substituted 2',3,4,4'-tetramethoxychalcones (alpha-X-TMCs, X = H, F, Cl, Br, I, CN, Me, p-NO2-C6H4, Ph, p-OMe-C6H4, NO2, CF3, COOEt, COOH) had proven to activate Nrf2 resulting in HO-1 induction and inhibit NF-kappa B downstream target genes, their protective effect against staurosporine induced apoptosis and reactive oxygen species (ROS) production was investigated. RAW264.7 macrophages treated with 19 different chalcones (15 alpha-X-TMCs, chalcone, 2'-hydroxychalcone, calythropsin and 2'-hydroxy-3,4,4'-trimethoxychalcone) prior to staurosporine treatment were analyzed for apoptosis and ROS production, as well as HO-1 protein expression and enzyme activity. Additionally, Nrf2 and NF-kappa B activity was assessed. We found that amongst all tested chalcones only E-alpha-(4-methoxyphenyl)-2',3,4,4'-tetramethoxychalcone (E-alpha-p-OMe-C6H4-TMC) demonstrated a distinct, statistically significant antiapoptotic effect in a dose dependent manner, showing no toxic effects, while its double bond isomer Z-alpha-p-OMe-C6H4-TMC displayed no significant activity. Also, E-alpha-p-OMe-C6H4-TMC induced HO-1 protein expression and increased HO-1 activity, whilst inhibition of HO-1 by SnPP-IX abolished its antiapoptotic effect. The only weakly electrophilic chalcone E-alpha-p-OMe-C6H4-TMC reduced the staurosporine triggered formation of ROS, while inducing the translocation of Nrf2 into the nucleus. Furthermore, staurosporine induced NF-kappa B activity was attenuated following E-alpha-p-OMe-C6H4-TMC treatment. Overall, E-alpha-p-OMe-C6H4-TMC demonstrated its effective cytoprotective potential via a non-toxic induction of HO-1 in RAW264.7 macrophages. The observed cytoprotective effect may partly be related to both, the activation of the Nrf2- and inhibition of the NF-kappa B pathway.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; HEME OXYGENASE-1; CARBON-MONOXIDE; BIOLOGICAL-ACTIVITY; MOLECULES; IDENTIFICATION; EXPRESSION; APOPTOSIS; STRESS; RAT; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) Chemistry and Pharmacy > Institut für Organische Chemie > Arbeitskreis Dr. Sabine Amslinger |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 May 2019 09:49 |
| Last Modified: | 07 May 2019 09:49 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4458 |
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