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 CO2 treatment 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’.