scholarly journals Complex Regulatory Interplay Between Multidrug Resistance and Oxidative Stress Response in Yeast: The FLR1 Regulatory Network as a Systems Biology Case-Study

10.5772/32603 ◽  
2012 ◽  
Author(s):  
Miguel C.
Keyword(s):  
Oxidative Stress ◽  
Multidrug Resistance ◽  
Systems Biology ◽  
Stress Response ◽  
Regulatory Network ◽  
Oxidative Stress Response ◽  
And Oxidative Stress

scholarly journals The bZip Transcription Factor Cap1p Is Involved in Multidrug Resistance and Oxidative Stress Response inCandida albicans

1999 ◽  
Vol 181 (3) ◽  
pp. 700-708 ◽  
Author(s):  
Anne-Marie Alarco ◽  
Martine Raymond
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Transcription Factor ◽  
Multidrug Resistance ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Bzip Transcription Factor ◽  
Term Therapy ◽  
Pathogenic Yeast ◽  
And Oxidative Stress

ABSTRACT Candida albicans is an opportunistic pathogenic yeast which frequently develops resistance to the antifungal agent fluconazole (FCZ) in patients undergoing long-term therapy. FCZ-resistant strains often display a reduced intracellular FCZ accumulation which correlates with the overexpression of the ATP-binding cassette transporters CDR1 and CDR2or the major facilitator (MF) MDR1. We have recently cloned a C. albicans gene, named CAP1, which codes for a bZip transcription factor of the AP-1 family homologous to the Yap1 protein involved in multidrug resistance and response to oxidative stress in Saccharomyces cerevisiae. CAP1 was found to confer FCZ resistance in S. cerevisiae by transcriptionally activating FLR1, a gene coding for an MF homologous to theC. albicans MDR1 gene product (A.-M. Alarco, I. Balan, D. Talibi, N. Mainville, and M. Raymond, J. Biol. Chem. 272:19304–19313, 1997). To study the role of CAP1 inC. albicans, we constructed a CAI4-derived mutant strain carrying a homozygous deletion of the CAP1 gene (CJD21). We found that deletion of CAP1 did not affect the susceptibility of CJD21 cells to FCZ, cerulenin, brefeldin A, and diamide but caused hypersensitivity to cadmium, 4-nitroquinolineN-oxide, 1,10-phenanthroline, and hydrogen peroxide, an effect which was reverted by reintroduction of the CAP1gene in these cells. Introduction of a hyperactive truncated allele ofCAP1 (CAP1-TR) in CJD21 resulted in resistance of the cells to all of the above compounds except hydrogen peroxide. The hyperresistant phenotype displayed by the CJD21 CAP1-TRtransformants was found to correlate with the overexpression of a number of potential CAP1 transcriptional targets such asMDR1, CaYCF1, CaGLR1, andCaTRR1. Taken together, our results demonstrate thatCAP1 is involved in multidrug resistance and oxidative stress response in C. albicans. Finally, disruption ofCAP1 in strain FR2, selected in vitro for FCZ resistance and constitutively overexpressing MDR1, did not suppress but rather increased the levels of MDR1 expression, demonstrating that CAP1 acts as a negative transcriptional regulator of the MDR1 gene in FR2 and is not responsible for MDR1 overexpression in this strain.

Metformin inhibits the inflammatory and oxidative stress response induced by skin UVB-irradiation and provides 4-hydroxy-2-nonenal and nitrotyrosine formation and p53 protein activation

2020 ◽  
Vol 100 (2) ◽  
pp. 152-155
Author(s):  
Fernando Pinheiro Souza-Neto ◽  
Poliana Camila Marinello ◽  
Gabriela Pasqual Melo ◽  
Leandra Zambeli Naira Ramalho ◽  
Eliana M. Cela ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
P53 Protein ◽  
Oxidative Stress Response ◽  
Uvb Irradiation ◽  
Protein Activation ◽  
And Oxidative Stress
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