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.

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

“…These results are in agreement with the general observation that PACAP KO mice are more vulnerable to tissue injuries than wild type mice [ 59 ]. This is also true for ischemic injuries.…”

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

“…in vivo decreased apoptosis, reduced expression of mcp-1, il-6, mip-2, myd88, tlr4, traf6, TRIF, IRF3 in primary mouse renal proximal tubule cells horvath et al [17] in vivo administration of pacap increased cell survival in primary rat kidney cell culture following H react more sensitively to various stressors [35], including ischemic lesions. pacap deficient mice displayed larger infarcted area in a model of focal cerebral ischemia and the extent of the ischemic retinal lesion was also increased [43].…”

“…it is suggested that endogenous pacap functions as a protective agent against different harmful stimuli [35,50]. Several studies have found that PACAP deficient mice Acta Biologica Hungarica 65, 2014 Table 1 summary of the protective effects of pacap in renal ischemia-reperfusion reference mode of investigation…”

Investigation of the Possible Functions of PACAP in Human Trophoblast Cells

“…PACAP knockout mice have decreased fertility, described in 82 numerous studies (Reglodi et al 2012a). This is in part due to 2003) in addition to other deficiencies described in mice 85 lacking endogenous PACAP (Reglodi et al 2012a).…”

“…This is in part due to 2003) in addition to other deficiencies described in mice 85 lacking endogenous PACAP (Reglodi et al 2012a). antibodies, and membranes necessary for the measurements.…”