Redox homeostasis dysregulation in noise-induced hearing loss: oxidative stress and antioxidant treatment

Table 1 Target proteins in the Nrf2-ARE pathway

Target proteins	Results	Mechanism	References
GSH synthetic enzymes↑ GSH regenerative enzymes↑	GSH↑	Increases GSH synthesis and regeneration, improves GSH levels	Stefanson et al. [113]
Glutamate cysteine ligase (GCL)↑	GSH↑	Upregulates two subunits of GCL, GCLC and GCLM, catalyzes the rate-limiting step in GSH synthesis	Shelly et al. [114]
HO-1↑	Heme↓	The inducible isoform of HO-1 removes the oxidation promoting molecule heme	Maines et al. [109]
HO-1↑	Bilirubin↑ Biliverdin↑	HO-1 decomposes heme to produce biliverdin and its reduction product bilirubin, both of which have antioxidant effects	Clark et al. [110]
NAD(P)H generating enzyme	NAD(P)H	Keap1 increases mitochondrial NADH pool	Holmström et al. [119]
NAD(P)H generating enzyme	NAD(P)H	Nrf2 expression of aldehyde dehydrogenase, generates NAD(P)H with NAD(P) as a cofactor	Dinkova-Kostova et al. [102]
Zn/Cu-SOD↑	Superoxide anion radicals↓	Nrf2 increases the level of Zn/Cu-SODs, Zn/Cu-SODs catalyze the disproportionation of superoxide anion radicals to generate oxygen and hydrogen peroxide	Tu et al. [105]

The symbol ↓ means the target factor level is reduced, and the symbol ↑ means the target factor level rises

ISSN: 1916-0216