3.5.7 Oxidative stress
Genes involved in regulating reactive oxygen species (ROS) and antioxidant production were differentially expressed in both issues; tf (CNS: upregulated and positively correlated with CO2 treatment and activity traits), cyb561d2 (CNS: downregulated), cbs (eyes: upregulated). Furthermore, scl4a11, which regulates the oxidative stress response, was positively correlated with CO2 treatment and activity traits in the CNS, and there was small, coordinated downregulation in the CNS of genes involved in ‘glutathione metabolic process’ (Table 6). Genes and functional categories involved in response to oxidative damage were also affected by CO2 treatment (Table 6). Genes involved in DNA repair were generally upregulated with CO2 treatment in the CNS; chrac1 was significantly upregulated, there was small, coordinated upregulation of ‘damaged DNA binding’ and ‘DNA repair’, spt16, foxm1, bptf, and arpc5 were positively correlated with COtreatment and activity traits, and nit1 , whose loss of expression promotes resistance to DNA damage stress, was negatively correlated with CO2 treatment and activity traits. Genes involved in protein damage control and endoplasmic reticulum stress were also affected by CO2 treatment; ykt6, which is essential for autophagy was upregulated in the CNS and eyes, and the heat shock protein hspa5, which is a key repressor of the unfolded protein response was positively correlated with CO2 treatment and activity traits. Furthermore, genes that induce apoptosis in response to DNA damage (apbb5) and ER stress (tmem214-b), were positively correlated with CO2 treatment and activity traits. There was also small, coordinated upregulation in the CNS of genes involved in the ‘regulation of apoptotic process’.