Mice deficient in neuropeptide PACAP demonstrate increased sensitivity to in vitro kidney hypoxia.
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.
Horvath
G
G
Department of Anatomy, University of Pecs, Pecs, Hungary. gabriella.horvath@aok.pte.hu
Racz
B
B
Szakaly
P
P
Kiss
P
P
Laszlo
E
E
Hau
L
L
Tamas
A
A
Helyes
Z
Z
Lubics
A
A
Hashimoto
H
H
Baba
A
A
Reglodi
D
D
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics; D016923:Cell Death; D002470:Cell Survival; D002531:Cerebellum / Q000473:pathology; D000860:Hypoxia / Q000235:genetics / Q000473:pathology; D007238:Infarction / Q000235:genetics; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018384:Oxidative Stress; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency*
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide