Glucose 6-phosphate dehydrogenase deficiency enhances germ cell apoptosis and causes defective embryogenesis in Caenorhabditis elegans

Yang, H-C; Chen, T-L; Wu, Y-H; Cheng, K-P; Lin, Y-H; Cheng, M-L; Ho, H-Y; Lo, S J; Chiu, D T-Y

It has been shown that G6PD knockdown enhances the inhibitory effect of H 2 O 2 on protein tyrosine phosphatase and causes sustained MAPK activation leading to cell demise. 13 In order to investigate whether MAPK played a role in G6PD knockdown-induced defective egg production, C. elegans MAPK mutants, including pmk-1, sek-1, and mek-1 were scored for their egg production under basal and G6PD knockdown conditions (Figures 6b-d) . Our results showed that pmk-1 mutant exhibited minor decrease of egg production compared to mock (91% of mock, Po0.001, n ¼ 70), whereas the egg production of the pmk-1/g6pd(RNAi) double mutant was similar to that of Gi C. elegans (P ¼ 0.136, n ¼ 70) (Figure 6b ). On the other hand, sek-1 mutant displayed reduced egg production similar to Gi C. elegans (76% of mock, Po0.001, n ¼ 70). Notably, sek-1/g6pd(RNAi) double mutant showed further decrease of egg production (42% of Gi C. elegans, Po0.001, n ¼ 70) (Figure 6c ). The mek-1 mutant displayed no difference of egg production compared with mock (P ¼ 0.334, n ¼ 60) (Figure 6d) . Also, the egg production of the mek-1/g6pd(RNAi) double mutant was indistinguishable to that of Gi C. elegans (P ¼ 0.471, n ¼ 60). Taken together, these results suggest that sek-1, but not mek-1 or pmk-1, acts in parallel to G6PD in the modulation of egg production.