One of the well-known effects of
pituitary adenylate cyclase activating polypeptide (
PACAP) is its neuroprotective and cytoprotective actions including renoprotective effects. Mice deficient in endogenous
PACAP exhibit several behavioral, metabolic, and developmental alterations. Furthermore,
PACAP-deficient mice have larger
infarct volume in a model of
cerebral ischemia, delayed axonal regeneration, and increased cell death in cerebellar oxidative stress. We have previously demonstrated that
PACAP-deficient mice have increased susceptibility to in vitro oxidative stress, which can be counteracted by exogenous
PACAP treatment. These results demonstrate that endogenous
PACAP has a protective role against various stressors. The objective of the present study was to investigate whether endogenous
PACAP has a protective effect in the kidney against in vitro
hypoxia. Kidney cell cultures were isolated from wild-type and
PACAP-deficient mice, and cell viability was assessed after in vitro
hypoxia induced using
CoCl(2). The sensitivity of cells from
PACAP-deficient mice was increased to
hypoxia: both after 24 and 48 hours of exposure, cell viability was significantly reduced compared with that in control wild-type mice. These results show that endogenous
PACAP protects against noxious stimuli in the kidney and that
PACAP may act as a stress sensor in renal cells.