HMOX1 and Hyperglycemia: Furthermore, the mRNA expression of NQO1 and HO1 showed a biphasic wave with initial up-regulation followed by down-regulation; this can be explained by the inference that Nrf2 was activated during hyperglycemia treatment and subsequent oxidative stress during the first 2 days, while it was eventually suppressed during 4- or 5-day hyperglycemia treatment with posttranslational modification due to long-term oxidative stress (Zhang et al., 2003; Thangarajah et al., 2009).