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Isocitrate dehydrogenase is important for nitrosative stress resistance in Cryptococcus neoformans, but oxidative stress resistance is not dependent on glucose-6-phosphate dehydrogenase.

Publication ,  Journal Article
Brown, SM; Upadhya, R; Shoemaker, JD; Lodge, JK
Published in: Eukaryot Cell
June 2010

The opportunistic intracellular fungal pathogen Cryptococcus neoformans depends on many antioxidant and denitrosylating proteins and pathways for virulence in the immunocompromised host. These include the glutathione and thioredoxin pathways, thiol peroxidase, cytochrome c peroxidase, and flavohemoglobin denitrosylase. All of these ultimately depend on NADPH for either catalytic activity or maintenance of a reduced, functional form. The need for NADPH during oxidative stress is well established in many systems, but a role in resistance to nitrosative stress has not been as well characterized. In this study we investigated the roles of two sources of NADPH, glucose-6-phosphate dehydrogenase (Zwf1) and NADP(+)-dependent isocitrate dehydrogenase (Idp1), in production of NADPH and resistance to oxidative and nitrosative stress. Deletion of ZWF1 in C. neoformans did not result in an oxidative stress sensitivity phenotype or changes in the amount of NADPH produced during oxidative stress compared to those for the wild type. Deletion of IDP1 resulted in greater sensitivity to nitrosative stress than to oxidative stress. The amount of NADPH increased 2-fold over that in the wild type during nitrosative stress, and yet the idp1Delta strain accumulated more mitochondrial damage than the wild type during nitrosative stress. This is the first report of the importance of Idp1 and NADPH for nitrosative stress resistance.

Duke Scholars

Published In

Eukaryot Cell

DOI

EISSN

1535-9786

Publication Date

June 2010

Volume

9

Issue

6

Start / End Page

971 / 980

Location

United States

Related Subject Headings

  • Sodium Nitrite
  • Oxidative Stress
  • Oxidation-Reduction
  • NADP
  • Microbiology
  • Isocitrate Dehydrogenase
  • Glucosephosphate Dehydrogenase
  • Cryptococcus neoformans
  • 3107 Microbiology
  • 11 Medical and Health Sciences
 

Citation

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Brown, S. M., Upadhya, R., Shoemaker, J. D., & Lodge, J. K. (2010). Isocitrate dehydrogenase is important for nitrosative stress resistance in Cryptococcus neoformans, but oxidative stress resistance is not dependent on glucose-6-phosphate dehydrogenase. Eukaryot Cell, 9(6), 971–980. https://doi.org/10.1128/EC.00271-09
Brown, Sarah M., Rajendra Upadhya, James D. Shoemaker, and Jennifer K. Lodge. “Isocitrate dehydrogenase is important for nitrosative stress resistance in Cryptococcus neoformans, but oxidative stress resistance is not dependent on glucose-6-phosphate dehydrogenase.Eukaryot Cell 9, no. 6 (June 2010): 971–80. https://doi.org/10.1128/EC.00271-09.

Published In

Eukaryot Cell

DOI

EISSN

1535-9786

Publication Date

June 2010

Volume

9

Issue

6

Start / End Page

971 / 980

Location

United States

Related Subject Headings

  • Sodium Nitrite
  • Oxidative Stress
  • Oxidation-Reduction
  • NADP
  • Microbiology
  • Isocitrate Dehydrogenase
  • Glucosephosphate Dehydrogenase
  • Cryptococcus neoformans
  • 3107 Microbiology
  • 11 Medical and Health Sciences