Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with
very diverse distribution and functions. Among others, PACAP is a potent cytoprotective
peptide due to its antiapoptotic, anti-inflammatory, and antioxidant actions. This
also has been shown in different kidney pathologies, including ischemia/reperfusion-induced
kidney injury. Similar protective effects of the endogenous PACAP are confirmed by
the increased vulnerability of PACAP-deficient mice to different harmful stimuli.
Kidneys of homozygous PACAP-deficient mice have more severe damages in renal ischemia/reperfusion
and kidney cell cultures isolated from these mice show increased sensitivity to renal
oxidative stress. In our present study we raised the question of whether the partial
lack of the PACAP gene is also deleterious, i.e. whether heterozygous PACAP-deficient
mice also display more severe damage after renal ischemia/reperfusion. Mice underwent
45 or 60 minutes of ischemia followed by 2 weeks reperfusion. Histological evaluation
of the kidneys was performed and individual histopathological parameters were graded.
Furthermore, we investigated apoptotic markers, cytokine expression, and the activity
of superoxide dismutase (SOD) enzyme 24 hours after 60 minutes of renal ischemia/reperfusion.
We found no difference between the intact kidneys of wild-type and heterozygous mice,
but marked differences could be observed following ischemia/reperfusion. Heterozygous
PACAP-deficient mice had more severe histological alterations, with significantly
higher histopathological scores for most of the tested parameters. Higher level of
the proapoptotic pp38 MAPK and of some proinflammatory cytokines, as well as lower
activity of the antioxidant SOD could be found in these mice. In conclusion, the partial
lack of the PACAP gene results in worse outcomes in cases of renal ischemia/reperfusion,
confirming that PACAP functions as an endogenous protective factor in the kidney.