Expression of PON2 isoforms varies among brain regions in male and female African green monkeys.

ABSTRACT

Mitochondrial dysfunction and oxidative stress contribute to the neuropathology of neurodegenerative disorders such as Parkinson's disease (PD). Paraoxonase-2 (PON2) is a mitochondrial protein that mitigates oxidative stress, enhances mitochondrial function and exhibits anti-inflammatory properties. Previously, we have documented sex-based variation in PON2 with higher brain PON2 expression in female (2-fold) as compared to male African green monkeys. This aim of this study is to identify PON2 isoforms and explore the region-based variations in the protein level of PON2 in brain of African green monkeys. Male and female brain tissue samples (striatum, hippocampus, occipital cortex, dorsolateral prefrontal cortex) from African green monkeys (Chlorocebus sabaeus) were analyzed by western blotting technique for PON2 expression. We found two PON2 isoforms (39 and 41 kDa) in each examined brain region of male and female monkeys. Male monkeys showed no significant difference in the expression level of PON2 isoforms among different brain regions whereas female monkeys showed a significant difference in the expression level of PON2 isoforms in all examined regions except dorsolateral prefrontal cortex. In addition, the result revealed highest expression of PON2 protein in striatum compared to other brain regions in both male and female monkeys. This report is the first to quantify expression of PON2 isoforms in different brain regions and it also establishes the existence of sex as well as region-based variation in PON2 protein expression in primate brain. Since PON2 serves a protective role for dopaminergic neurons it should be considered as a druggable target for oxidative stress-related neurodegenerative disorders like PD. We anticipate that the outcome of this study will contribute to the development of neuroprotective strategies in PD.