TY  - JOUR
A1  - Ferber, Elena
A1  - Gerhards, Julian
A1  - Sauer, Miriam
A1  - Krischke, Markus
A1  - Dittrich, Marcus T.
A1  - Müller, Tobias
A1  - Berger, Susanne
A1  - Fekete, Agnes
A1  - Mueller, Martin J.
T1  - Chemical Priming by Isothiocyanates Protects Against Intoxication by Products of the Mustard Oil Bomb
JF  - Frontiers in Plant Science
N2  - In Brassicaceae, tissue damage triggers the mustard oil bomb i.e., activates the degradation of glucosinolates by myrosinases leading to a rapid accumulation of isothiocyanates at the site of damage. Isothiocyanates are reactive electrophilic species (RES) known to covalently bind to thiols in proteins and glutathione, a process that is not only toxic to herbivores and microbes but can also cause cell death of healthy plant tissues. Previously, it has been shown that subtoxic isothiocyanate concentrations can induce transcriptional reprogramming in intact plant cells. Glutathione depletion by RES leading to breakdown of the redox potential has been proposed as a central and common RES signal transduction mechanism. Using transcriptome analyses, we show that after exposure of Arabidopsis seedlings (grown in liquid culture) to subtoxic concentrations of sulforaphane hundreds of genes were regulated without depletion of the cellular glutathione pool. Heat shock genes were among the most highly up-regulated genes and this response was found to be dependent on the canonical heat shock factors A1 (HSFA1). HSFA1-deficient plants were more sensitive to isothiocyanates than wild type plants. Moreover, pretreatment of Arabidopsis seedlings with subtoxic concentrations of isothiocyanates increased resistance against exposure to toxic levels of isothiocyanates and, hence, may reduce the autotoxicity of the mustard oil bomb by inducing cell protection mechanisms.
KW  - autotoxicity
KW  - heat shock response
KW  - isothiocyanates
KW  - mustard oil bomb
KW  - reactive electrophilic species
KW  - redox homeostasis
KW  - sulforaphane
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207104
SN  - 1664-462X
VL  - 11
ER  - 
TY  - JOUR
A1  - Adam, Christian
A1  - Baeurle, Anne
A1  - Brodsky, Jeffrey L.
A1  - Schrama, David
A1  - Wipf, Peter
A1  - Becker, Jürgen Christian
A1  - Houben, Roland
T1  - The HSP70 Modulator MAL3-101 Inhibits Merkel Cell Carcinoma
N2  - Merkel Cell Carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer for which no effective treatment is available. MCC represents a human cancer with the best experimental evidence for a causal role of a polyoma virus. Large T antigens (LTA) encoded by polyoma viruses are oncoproteins, which are thought to require support of cellular heat shock protein 70 (HSP70) to exert their transforming activity. Here we evaluated the capability of MAL3-101, a synthetic HSP70 inhibitor, to limit proliferation and survival of various MCC cell lines. Remarkably, MAL3-101 treatment resulted in considerable apoptosis in 5 out of 7 MCC cell lines. While this effect was not associated with the viral status of the MCC cells, quantitative mRNA expression analysis of the known HSP70 isoforms revealed a significant correlation between MAL3-101 sensitivity and HSC70 expression, the most prominent isoform in all cell lines. Moreover, MAL3-101 also exhibited in vivo antitumor activity in an MCC xenograft model suggesting that this substance or related compounds are potential therapeutics for the treatment of MCC in the future.
KW  - apoptosis
KW  - cancer treatment
KW  - cell staining
KW  - cultured fibroplasts
KW  - heat shock response
KW  - membrans proteins
KW  - polymerase chain reaction
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-112795
ER  -