Effects of PACAP on mitochondrial apoptotic pathways and cytokine expression in rats subjected to renal ischemia/reperfusion.

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with highly efficient cytoprotective actions. Its neuroprotective effects are well-known, but PACAP is able to exert similar actions in non-neuronal cells. Recently, we have shown that PACAP prolongs renal ischemic time, decreases mortality, and attenuates tubular degeneration in a rat model of renal ischemia/reperfusion, but the mechanism of renoprotection is not yet known. Therefore, the aim of the present study was to obtain further insight into the renoprotective effects of PACAP by examining its direct effects of PACAP on mitochondrial permeability transition in vitro and on the expression of the anti-apoptotic Bcl-2 and cytokines/chemokines in kidney tissues following 45 and 60 min renal ischemia and reperfusion in vivo. We found that PACAP did not have any direct effect on mitochondrial permeability transition. Cytokine array revealed that the expression of a few cytokines/chemokines was strongly increased after ischemia/reperfusion, which was ameliorated by PACAP treatment. Furthermore, in rats subjected to renal ischemia, PACAP treatment counteracted the ischemia/reperfusion-induced decrease of the anti-apoptotic Bcl-2, both after 45 and 60 min ischemia, as analyzed by Western blot. In summary, we showed that PACAP could attenuate tissue injury involving both anti-inflammatory and anti-apoptotic effects, but not directly acting on mitochondrial permeability transition.