In vivo protein transduction: Penetration of the biologically active HIV-1 tat mediated Cu,Zn-superoxide dismutase rescues murine skin from oxidative stress

Reactive oxygen species (ROS), derived from the metabolism of oxygen and exist inherently in all aerobic organisms, lead to oxidative damage in a cell, tissue, or organ. This damage can affect a specific molecule or the entire organism. The level of oxidative stress is determined by the balance between the rate at which oxidative damage is induced and the rate at which it is efficiently repaired and removed. Antioxidant enzymes, such as superoxide dismutase (SOD) have been encouraging to have a beneficial effect against various diseases mediated by the ROS. We have reported that the denatured Tat-SOD1 was successfully transduced into PC12 cells in vitro and retained its activity which rescued the cells from paraquat-induced oxidative stress. We assess the ability of in vivo delivery of Tat-SOD1 fusion protein into the mammalian. The sodium nitroferricyanide (SNP)-induced expressions of COX-2 and nitroxide were reduced by the presence of Tat-SOD1 protein. Our results demonstrated that Tat-SOD1 proteins efficiently penetrated into the epidermis and the dermis of murine skin, moreover, successfully inactivated the induced oxidative damage. In vivo transduction of functioning protein may open the door to protein therapy for human diseases related to this antioxidant enzyme and to ROS.