The Anopheles gambiae oxidation resistance 1 (OXR1) gene regulates expression of enzymes that detoxify reactive oxygen species.
BACKGROUND
OXR1 is an ancient gene, present in all eukaryotes examined so far that confers protection from oxidative stress by an unknown mechanism. The most highly conserved region of the gene is the carboxyl-terminal TLDc domain, which has been shown to be sufficient to prevent oxidative damage.


RESULTS
OXR1 has a complex genomic structure in the mosquito A. gambiae, and we confirm that multiple splice forms are expressed in adult females. Our studies revealed that OXR1 regulates the basal levels of catalase (CAT) and glutathione peroxidase (Gpx) expression, two enzymes involved in detoxification of hydrogen peroxide, giving new insight into the mechanism of action of OXR1. Gene silencing experiments indicate that the Jun Kinase (JNK) gene acts upstream of OXR1 and also regulates expression of CAT and GPx. Both OXR1 and JNK genes are required for adult female mosquitoes to survive chronic oxidative stress. OXR1 silencing decreases P. berghei oocyst formation. Unexpectedly, JNK silencing has the opposite effect and enhances Plasmodium infection in the mosquito, suggesting that JNK may also mediate some, yet to be defined, antiparasitic response.


CONCLUSIONS
The JNK pathway regulates OXR1 expression and OXR1, in turn, regulates expression of enzymes that detoxify reactive oxygen species (ROS) in Anopheles gambiae. OXR1 silencing decreases Plasmodium infection in the mosquito, while JNK silencing has the opposite effect and enhances infection.
Jaramillo-Gutierrez
Giovanna
G
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Molina-Cruz
Alvaro
A
Kumar
Sanjeev
S
Barillas-Mury
Carolina
C
D000818:Animals; D000852:Anopheles / Q000235:genetics*; D002374:Catalase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D020868:Gene Silencing; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*
D019476:Insect Proteins; D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase