0000000000309012
AUTHOR
Renate V. Bardeleben
The HMG-CoA reductase inhibitor lovastatin protects cells from the antineoplastic drugs doxorubicin and etoposide
Ras-homologous GTPases are involved in the regulation of genotoxic stress-induced gene expression and cell death. Since they need C-terminal isoprenylation for correct intracellular localization and function, we investigated whether depletion of cells from isopren precursor moieties using the HMG-CoA reductase inhibitor lovastatin affects cellular sensitivity to DNA damaging drugs. Here we show that lovastatin renders cells highly resistant to the tumor-therapeutic compound doxorubicin. Desensitization by lovastatin was reverted by co-treatment with GGPP indicating that inhibition of protein geranylgeranylation is involved in acquired doxorubicin resistance. Lovastatin does not influence ce…
Transnational Precursors of American Realism
This chapter concentrates on European realist innovators—Björnstjerne Björnson, Ivan Turgenev, Leo Tolstoy, Fyodor Dostoevsky, Honoré de Balzac, Gustave Flaubert, Guy de Maupassant—and their effect on the formative period of American realism. It studies in detail the transatlantic development of new techniques and discusses the ways in which these new methods were reflected in the works of American authors and critics. Inspired by the theories and practice of their precursors, American writers felt liberated to introduce new narrative strategies to represent America’s rising urbanism, the struggles of the social classes, and the increase of social mobility in the industrial age. They also d…
Ultraviolet light-induced apoptotic death is impaired by the HMG-CoA reductase inhibitor lovastatin.
HMG-CoA reductase inhibitors (i.e., statins) attenuate C-terminal isoprenylation of Rho GTPases, thereby inhibiting UV-C-induced activation of c-Jun-N-terminal kinases/stress-activated protein kinases (JNKs/SAPKs). Inhibition of UV-C-triggered JNK/SAPK activation by lovastatin is due to inhibition of Rac-SEK1/MKK4-mediated phosphorylation of JNKs/SAPKs at Thr183/Tyr185. UV-C-stimulated phosphorylation of p38 kinase (Thr180/Tyr182) is also impaired by lovastatin. Cell killing provoked by UV-C irradiation was significantly inhibited by lovastatin. This was paralleled by a reduced frequency of chromosomal aberrations, accelerated recovery from UV-C-induced transient replication blockage, inhib…