PACAP Enhances Barrier Properties of Cerebral Microvessels

Wilhelm, Imola; Fazakas, Csilla; Tamás, Andrea; Tóth, Gábor; Reglődi, Dóra; Krizbai, István A.

doi:10.1007/s12031-014-0260-4

Cited by 15 publications

(12 citation statements)

References 30 publications

(31 reference statements)

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“…Altogether, these fi ndings show that both peptides counteract high glucose + IL-1β-induced damage in ARPE19 cells, suggesting that they might be relevant to the maintenance of outer blood-retinal barrier function in edema accompanying diabetic retinopathy [ 55 ]. These results are in accordance with our earlier observations in an in vitro blood-brain barrier (BBB) model [ 56 ]. We found that PACAP treatment improved the barrier properties of the brain endothelium.…”

Section: In Vitro Protective Effects In the Retinal Pigment Epitheliasupporting

confidence: 92%

“…PACAP induced an increase in the transendothelial electrical resistance, which is the most important marker of the tightness of the tight junctions. Moreover, PACAP had a protective role against glucose deprivation-and oxidative stressinduced junctional damage in microvascular brain endothelial cells [ 56 ].…”

Section: In Vitro Protective Effects In the Retinal Pigment Epitheliamentioning

confidence: 96%

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Protective Effects of PACAP in the Retina

Atlasz

Vaczy

Werling

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a widespread neuropeptide that is well known for its general cytoprotective effects in different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors also occur in the retina. In this review, we summarize the retinoprotective effects of PACAP. In vitro, PACAP is protective against glutamate, thapsigargin, anisomycin, oxidative stress, UV light, high glucose, infl ammation, and anoxia. Both the neural retina and the pigment epithelial cells can be protected by PACAP in various experimental paradigms. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models in rats and mice: excitotoxic injury induced by glutamate, N -methyl-D -aspartate (NMDA) or kainate, ischemic injury induced by carotid artery ligation and high intraocular pressure, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy as well as retinopathy of prematurity. Molecular biological methods have revealed that PACAP activates anti-apoptotic, while inhibits pro-apoptotic signaling pathways, and it also stimulates an anti-infl ammatory environment in the retina. Altogether, PACAP is suggested to be a potential therapeutic retinoprotective agent in various retinal diseases.

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Section: In Vitro Protective Effects In the Retinal Pigment Epitheliasupporting

confidence: 92%

Section: In Vitro Protective Effects In the Retinal Pigment Epitheliamentioning

confidence: 96%

Protective Effects of PACAP in the Retina

Atlasz

Vaczy

Werling

et al. 2016

Current Topics in Neurotoxicity

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“…Therefore, given its contribution to age-related brain vulnerabilities, large efforts are underway to restore BBB function. In this regard, the pituitary adenylate cyclaseactivating polypeptide was found to strikingly improve transendothelial electrical resistance and BBB tightness, as well as to protect against glucose deprivation and oxidative stress-induced junctional damage [137].…”

Section: Impairment Of Blood-brain Barrier Properties In Agingmentioning

confidence: 99%

Dissecting the Contribution of Vascular Alterations and Aging to Alzheimer’s Disease

2015

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Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive decline that afflicts as many as 45 % of individuals who survive past the age of 85. AD has been associated with neurovascular dysfunction and brain accumulation of amyloid-β peptide, as well as tau phosphorylation and neurodegeneration, but the pathogenesis of the disease is still somewhat unclear. According to the amyloid cascade hypothesis of AD, accumulation of amyloid-β peptide (Aβ) aggregates initiates a sequence of events leading to neuronal injury and loss, and dementia. Alternatively, the vascular hypothesis of AD incorporates the vascular contribution to the disease, stating that a primary insult to brain microcirculation (e.g., stroke) not only contributes to amyloidopathy but initiates a non-amyloidogenic pathway of vascular-mediated neuronal dysfunction and injury, which involves blood-brain barrier compromise, with increased permeability of blood vessels, leakage of blood-borne components into the brain, and, consequently, neurotoxicity. Vascular dysfunction also includes a diminished brain capillary flow, causing multiple focal ischemic or hypoxic microinjuries, diminished amyloid-β clearance, and formation of neurotoxic oligomers, which lead to neuronal dysfunction. Here we present and discuss relevant findings on the contribution of vascular alterations during aging to AD, with the hope that a better understanding of the players in the "orchestra" of neurodegeneration will be useful in developing therapies to modulate the "symphony".

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“…Besides its general cell protective, prosurvival, and anti‐inflammatory effects, PACAP might possess protective effects on TJs of endothelial and epithelial cells . PACAP stabilizes the junctional proteins in the membrane of brain endothelial cells both in control and in pathological conditions (e.g., glucose deprivation and oxidative stress) . Moreover, PACAP was shown to have a protective effect on the barrier properties of the cells of the o‐BRB in the presence of factors accounting for diabetic macular edema (i.e., high glucose and interleukin‐1β) .…”

Section: Introductionmentioning

confidence: 99%

Pituitary adenylate cyclase activating polypeptide acts against neovascularization in retinal pigment epithelial cells

Fábián

Reglődi

Horváth

et al. 2019

Annals of the New York Academy of Sciences

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The purpose of this study was to determine whether pituitary adenylate cyclase activating polypeptide (PACAP) could influence the neovascularization processes in hyperosmotic and oxidative stress in retinal pigment epithelial cells. Hyperosmotic conditions and oxidative stress were induced by 200 mM sucrose and 250 μM hydrogen peroxide (H 2 O 2 ), respectively. Morphology and elasticity of adult retinal pigment epithelial (ARPE-19) cells were measured by atomic force microscopy, while the investigation of junctional molecules, such as occludin and ZO-1, was carried out using immunofluorescence. For cell viability measurement, the MTT test was used. The effect of PACAP on the key angiogenic factors, such as vascular endothelial growth factor, angiogenin, and endothelin-1, was measured by an angiogenesis array and flow cytometry. Hyperosmotic stress-induced reorganization of the cytoskeleton and impairment of the junctions decreased cell viability and upregulated several angiogenic factors. In oxidative stress, we found that opening of the junctions decreased viability and upregulated the expression of angiogenic factors. PACAP was shown to be protective in both conditions. Retinal pigment epithelium cells play an important role in several diseases, such as diabetic retinopathy and macular edema. Therefore, protecting retinal pigment epithelial (RPE) cells with PACAP could be a novel and potential treatment in these diseases.

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PACAP Enhances Barrier Properties of Cerebral Microvessels

Cited by 15 publications

References 30 publications

Protective Effects of PACAP in the Retina

Protective Effects of PACAP in the Retina

Dissecting the Contribution of Vascular Alterations and Aging to Alzheimer’s Disease

Pituitary adenylate cyclase activating polypeptide acts against neovascularization in retinal pigment epithelial cells

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