Oxidative stress induces different tissue dependent effects on Mutyh-deficient mice.

摘要: 8-oxoguanine (8-oxoG) is one of the most prevalent genotoxic lesions, and it generated in DNA attacked by reactive oxygen species (ROS). Adenine misincorporated opposite to 8-oxoG during replication excised MutY homolog (MUTYH), an important protein base excision repair (BER) system. Mutyh plays role maintenance genomic integrity, but functional consequences deficiency are not fully understood. In current study, we investigated histological changes five tissues (hippocampus, heart, liver, kidney lung) their molecular basis Mutyh-/- wild-type mice exposed D-galactose (D-gal). Our data indicated that hindered weight gain experimental induced substantial alterations content superoxide dismutase (SOD) activity, no significant impairment appeared Mutyh- deficient without D-gal exposure. Under low-dose exposure, altered expression genes involved mitochondrial unfolded response (UPRmt) liver lung, caused enhanced dynamics proteins (MDPs) hippocampus liver. The stress responses could maintain proteostasis function. However, such were noted when experiencing excessive damage burden high-dose which increased accumulation aggravated mitonuclear imbalance, as well lesions kidney. A higher sensitivity ROS-induced cardiotoxicity with exposure was noticed mice. differences learning memory impairments observed between conclusion, our demonstrated has different impacts on various based degree oxidative stress.