title: PACAP is an endogenous protective factor-insights from PACAP-deficient mice.
abstract: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widespread neuropeptide with a diverse array of biological functions. Not surprisingly, the lack of endogenous PACAP therefore results in a variety of abnormalities. One of the important effects of PACAP is its neuroprotective and general cytoprotective role. PACAP protects neurons and other tissues against ischemic, toxic, and traumatic lesions. Data obtained from PACAP-deficient mice provide evidence that endogenous PACAP also has protective functions. Mice lacking PACAP are more vulnerable to different in vitro and in vivo insults. The present review summarizes data on the increased sensitivity of PACAP-deficient mice against harmful stimuli. Mice lacking PACAP respond with a higher degree of injury in cerebral ischemia, autoimmune encephalomyelitis, and axonal lesion. Retinal ischemic and excitotoxic injuries also produce increased cell loss in PACAP-deficient mice. In peripheral organs, kidney cell cultures from PACAP-deficient mice are more sensitive to oxidative stress and in vitro hypoxia. In vivo, PACAP-deficient mice have a negative histological outcome and altered cytokine response in kidney and small intestine ischemia/reperfusion injury. Large intestinal inflammation, toxic lesion of the pancreas, and doxorubicin-induced cardiomyopathy are also more severe with a lack of endogenous PACAP. Finally, an increased inflammatory response has been described in subacute endotoxin-induced airway inflammation and in an oxazolone-induced allergic contact dermatitis model. In summary, lack of endogenous PACAP leads to higher vulnerability in a number of injuries in the nervous system and peripheral organs, supporting the hypothesis that PACAP is part of the endogenous cytoprotective machinery.
authors.affiliation: Department of Anatomy, PTE-MTA Lendulet PACAP Research Group, University of Pecs, 7624 Pecs, Szigeti u 12, Hungary. dora.reglodi@aok.pte.hu
authors.forename: D
authors.initials: D
authors.lastname: Reglodi
authors.forename: P
authors.initials: P
authors.lastname: Kiss
authors.forename: K
authors.initials: K
authors.lastname: Szabadfi
authors.forename: T
authors.initials: T
authors.lastname: Atlasz
authors.forename: R
authors.initials: R
authors.lastname: Gabriel
authors.forename: G
authors.initials: G
authors.lastname: Horvath
authors.forename: P
authors.initials: P
authors.lastname: Szakaly
authors.forename: B
authors.initials: B
authors.lastname: Sandor
authors.forename: A
authors.initials: A
authors.lastname: Lubics
authors.forename: E
authors.initials: E
authors.lastname: Laszlo
authors.forename: J
authors.initials: J
authors.lastname: Farkas
authors.forename: A
authors.initials: A
authors.lastname: Matkovits
authors.forename: R
authors.initials: R
authors.lastname: Brubel
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.forename: A
authors.initials: A
authors.lastname: Ferencz
authors.forename: A
authors.initials: A
authors.lastname: Vincze
authors.forename: Z
authors.initials: Z
authors.lastname: Helyes
authors.forename: L
authors.initials: L
authors.lastname: Welke
authors.forename: A
authors.initials: A
authors.lastname: Lakatos
authors.forename: A
authors.initials: A
authors.lastname: Tamas
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology; D009202:Cardiomyopathies / Q000503:physiopathology; D017449:Dermatitis, Allergic Contact / Q000503:physiopathology; D004198:Disease Susceptibility; D006706:Homeostasis / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology; D008171:Lung Diseases / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity; D009676:Noxae / Q000009:adverse effects; D010182:Pancreatic Diseases / Q000503:physiopathology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013312:Stress, Physiological / Q000502:physiology*; D014947:Wounds and Injuries / Q000503:physiopathology
chemical_list: C495402:Adcyap1 protein, mouse; D009498:Neurotoxins; D009676:Noxae; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide