Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling

Yen, Wei-Chen; Wu, Yi-Hsuan; Wu, Chih-Ching; Lin, Hsin-Ru; Stern, Arnold; Chen, Shih-Hsiang; Shu, Jwu-Ching; Tsun-Yee Chiu, Daniel

Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is perhaps the most common sex-linked enzymopathy on earth [1] , the biochemical and physiologic roles of this housekeeping enzyme have not been fully explored [2] . Biochemically, G6PD is well known as the rate-limiting enzyme of the pentose phosphate pathway for regenerating nicotinamide adenine dinucleotide phosphate (NADPH) [3] [4] [5] [6] . NADPH, an essential cofactor in the redox system, maintains a proper level of reducing equivalence such as reduced glutathione (GSH) and acts as a substrate for NADPH oxidase (NOX) and nitric oxide synthase (NOS), which generate reactive oxygen species (ROS) and nitric oxide (NO), respectively, for a subsequent role in signal transduction [1, 7, 8] . Physiologically, evidence has been emerging to indicate that G6PD deficiency affects glucose metabolism [9] , cell growth, embryonic development, lethality [10, 11] and susceptibility to infections by modulating redox homeostasis [12, 13] .