Involvement of the pleiotropic drug resistance response, protein kinase C signaling, and altered zinc homeostasis in resistance of Saccharomyces cerevisiae to diclofenac.

ABSTRACT: Diclofenac is a widely used analgesic drug that can cause serious adverse drug reactions. We used Saccharomyces cerevisiae as a model eukaryote with which to elucidate the molecular mechanisms of diclofenac toxicity and resistance. Although most yeast cells died during the initial diclofenac treatment, some survived and started growing again. Microarray analysis of the adapted cells identified three major processes involved in diclofenac detoxification and tolerance. In particular, pleiotropic drug resistance (PDR) genes and genes under the control of Rlm1p, a transcription factor in the protein kinase C (PKC) pathway, were upregulated in diclofenac-adapted cells. We tested if these processes or pathways were directly involved in diclofenac toxicity or resistance. Of the pleiotropic drug r

SUBMITTER: van Leeuwen JS 

PROVIDER: S-EPMC3165418 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature