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

e damage may be limited in playing a role in enhanced germ cell apoptosis caused by G6PD deficiency. As p53-dependent DNA damage pathway 35 and G6PD knockdown-induced alteration in MAPK activity are associated with cell demise, 13 loss-of-function mutants of C. elegans p53 (cep-1) and MAPK pathways (pmk-1, sek-1 and mek-1) are scored for their egg production ( Figure 6 ) and hatching (Figure 7 ) upon G6PD knockdown. The interpretation of the genetic analysis suggests that cep-1 is not required for the maintenance of normal egg production (Figure 6a ). On the other hand, the p38 MAPK pathway, including pmk-1 and sek-1, is required for the maintenance of normal egg production (Figures 6b and c) . As G6PD knockdown cannot further decrease egg production in pmk-1 mutant, this indicates that pmk-1 may act downstream of g6pd in the same pathway for maintaining normal egg production (Figure 6b ). While mek-1 is not involved in the maintenance of normal egg production (Figure 6d) , the additive suppression of egg production in sek-1/g6pd(RNAi) double mutant suggests that sek-1 may function in parallel to g6pd rather than in the same pathway (Figure 6c ). In general, p38 MAPK pathway is associated with diverse cellular functions, including immunity, apoptosis, stress response, and cell fate determination. The C. elegans pmk-1, a human p38 MAPK homologue, is activated by the mammalian MKK3/6 homologue sek-1, a member of MAPKK, which is downstream of nsy-1. The nsy-1-sek-1-pmk-1 cascade of p38 MAPK signaling is essential in the environmental response in C. elegans. 36 In addition, the C. elegans mek-1, a member of MAPK kinase (MAPKK) and activator of c-Jun N-terminal kinase (JNK), is also involved in stress response. 37 Hence, our results indicate that MAPK pathway is not directly associated with G6PD knockdown-induced defective egg production in C. elegans.