Influence of Terminal Differentiation and PACAP on the Cytokine, Chemokine, and Growth Factor Secretion of Mammary Epithelial Cells

Citation: Werling D, Reglodi D, Banks WA, et al. Ocular delivery of PACAP1-27 protects the retina from ischemic damage in rodents. Invest Ophthalmol Vis Sci. 2016;57:6683-6691. DOI: 10.1167/iovs.16-20630 PURPOSE. Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in neuronal injuries. Bilateral common carotid artery occlusion (BCCAO) causes chronic hypoperfusion-induced degeneration in the rat retina, where we proved the retinoprotective effect of intravitreal PACAP. Although this route of administration is a common clinical practice in several diseases, easier routes are clinically important. Our aim was to investigate the potential retinoprotective effects of PACAP eye drops in BCCAO-induced ischemic retinopathy.METHODS. After performing BCCAO in rats, the right eyes were treated with PACAP1-27 eye drops (1 lg/drop, 2 3 1 drops/day for 5 days), containing different vehicles: saline, water for injections, thiomersal or benzalkonium solution for ophthalmic use (SOCB). Histology and immunohistochemistry were performed 2 weeks after surgery, while molecular analysis was performed 24 hours after BCCAO. Passage of PACAP1-27 through the ocular layers was tested with radioactive PACAP-SOCB in mice.RESULTS. Bilateral common carotid artery occlusion led to a severe degeneration of all retinal layers. Solution for ophthalmic use was the most effective vehicle for delivering PACAP (PACAP-SOCB), significantly ameliorating BCCAO-induced damage. The massive upregulation of GFAP was not observed in retinas treated with PACAP-SOCB eye drops. PACAP-SOCB treatment also increased activation of the protective Akt and ERK1/2 in hypoperfused retinas. The cytokine profile showing upregulation in different cytokines was attenuated by PACAP-SOCB. Radioactive PACAP reached the retina when delivered in SOCB-containing eye drops.CONCLUSIONS. PACAP1-27, delivered in the SOCB vehicle as eye drops, was retinoprotective in ischemic retinopathy, providing the basis for future therapeutic administration.

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“…Pixel volumes of the spot of interest were normalized to the control (sham retinas). 26 The array was repeated four times.…”

Section: Cytokine Arraymentioning

confidence: 99%

Ocular Delivery of PACAP1-27 Protects the Retina From Ischemic Damage in Rodents

Werling

Reglődi

Banks

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…Lack of PACAP also influences behavior of these animals (Farkas et al 2017), and results in alterations of neuronal development (Rivnyak et al 2018). Not only the absence of the neuropeptide but its addition also affects the differentiation of chondrocytes (Juhasz et al 2014a), neurons (Guo et al 2016), and mammary epithelial cells (Csanaky et al 2014). We have demonstrated earlier that PACAP increases Ca 2+ release in osteoblasts and induces their differentiation (Juhasz et al 2014b).…”

Section: Discussionmentioning

confidence: 92%

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

et al. 2019

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a naturally secreted signaling peptide and has important regulatory roles in the differentiation of the central nervous system and its absence results in disorders in femur development. PACAP has an important function in prevention of oxidative stress or mechanical stress in chondrogenesis but little is known about its function in bone regeneration. A new callus formation model was set to investigate its role in bone remodeling. Fracturing was 5 mm distal from the proximal articular surface of the tibia and the depth was 0.5 mm. Reproducibility of callus formation was investigated with CT 3, 7, and 21 days after the operation. Absence of PACAP did not alter the alkaline phosphatase (ALP) activation in PACAP KO healing process. In developing callus, the expression of collagen type I increased in wild-type (WT) and PACAP KO mice decreased to the end of healing process. Expression of the elements of BMP signaling was disturbed in the callus formation of PACAP KO mice, as bone morphogenic protein 4 (BMP4) and 6 showed an early reduction in bone regeneration. However, elevated Smad1 expression was demonstrated in PACAP KO mice. Our results indicate that PACAP KO mice show various signs of disturbed bone healing and suggest PACAP compensatory and fine tuning effects in proper bone regeneration.

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“…We demonstrated that PACAP had no effect on cell differentiation, as PACAP treatment did not infl uence the β-casein expression. Mouse cytokine and angiogenesis arrays were also used to show the PACAP-induced changes in secreted cytokines, growth and angiogenic factors in differentiated and non-differentiated cells, where PACAP was able to decrease the levels of amphiregulin and epidermal growth factor, which may have physiological implications in the development and progression of mammary gland diseases [ 45 ].…”

Section: Abstract Pacap-like Immunoreactivity • Milk • Lactation • Mamentioning

confidence: 99%

Examination of PACAP During Lactation

Tamás

Vass

Helyes³

et al. 2016

Current Topics in Neurotoxicity

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Breast milk is a complex biological fl uid that contains nutritional components and non-nutritive bioactive factors promoting survival and healthy development of the newborn. PACAP has important functions, as a bioactive factor, in reproductive and developmental processes. Shortly after its discovery, PACAP and its receptors were identifi ed in normal and cancerous mammary gland samples. The present review summarizes data obtained in breast milk during different periods of lactation by radioimmunoassay. Our group showed, for the fi rst time, that PACAP is present in the human milk at levels 5-to 20-fold higher than in the respective plasma samples. PACAP-like immunoreactivity (LI) is higher in colostrum compared to transitional and mature human milk samples. PACAP level seems stable until the 10th month of lactation and there after, a signifi cant increase can be observed between samples obtained in the interval 11th-17th months of breastfeeding. The presence of PACAP can also be confi rmed in milk and plasma samples from the most commonly used ruminant domestic animals (cow, sheep and goat), pasteurized cow milk and infant formula samples. Similarly to the human results, the concentration of PACAP in the milk whey is almost ten times higher than in the plasma of the respective animals, while pasteurized cow milk and infant formula samples contain PACAP-LI levels comparable to human milk samples. The exact function of PACAP in the milk is not known at the moment. We hypothesize that PACAP (1) is essential for the growth and development of the

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Influence of Terminal Differentiation and PACAP on the Cytokine, Chemokine, and Growth Factor Secretion of Mammary Epithelial Cells

Cited by 13 publications

References 54 publications

Ocular Delivery of PACAP1-27 Protects the Retina From Ischemic Damage in Rodents

Ocular Delivery of PACAP1-27 Protects the Retina From Ischemic Damage in Rodents

Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation

Examination of PACAP During Lactation

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