ArticleJournal of molecular neuroscience : MN2012
Effects of PACAP on intracellular signaling pathways in human retinal pigment epithelial cells exposed to oxidative stress.
Article in Journal of molecular neuroscience : MN, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Articular cartilage thickness alterations in hind limb of young and aged PAC1 gene-deficient mice.Cell and tissue research · 2026Article
- Investigation of PACAP38 and PAC1 Receptor Expression in Human Retinoblastoma and the Effect of PACAP38 Administration on Human Y-79 Retinoblastoma Cells.Life (Basel, Switzerland) · 2024Article
- Mechanistic insights into the alterations and regulation of the AKT signaling pathway in diabetic retinopathy.Cell death discovery · 2023Review
- Expression of Oxidative Stress and Inflammation-Related Genes in Nasal Mucosa and Nasal Polyps from Patients with Chronic Rhinosinusitis.International journal of molecular sciences · 2022Article
- Effects of Pituitary Adenylate Cyclase Activating Polypeptide on Cell Death.International journal of molecular sciences · 2022Review
- PACAP and NAP: Effect of Two Functionally Related Peptides in Diabetic Retinopathy.Journal of molecular neuroscience : MN · 2021Review
- Stability Test of PACAP in Eye Drops.Journal of molecular neuroscience : MN · 2021Article
- Protective Effects of PACAP in Peripheral Organs.Frontiers in endocrinology · 2020Review
- Pituitary Adenylate Cyclase-activating Polypeptides Prevent Hepatocyte Damage by Promoting Yes-associated Protein in Liver Ischemia-Reperfusion Injury.Transplantation · 2019Article
- Spatiotemporal Expression Changes of PACAP and Its Receptors in Retinal Ganglion Cells After Optic Nerve Crush.Journal of molecular neuroscience : MN · 2019Article
- Retinoprotective Effects of TAT-Bound Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Polypeptide.Journal of molecular neuroscience : MN · 2019Article
- PACAP Attenuates Optic Nerve Crush-Induced Retinal Ganglion Cell Apoptosis Via Activation of the CREB-Bcl-2 Pathway.Journal of molecular neuroscience : MN · 2019Article
- Passage through the Ocular Barriers and Beneficial Effects in Retinal Ischemia of Topical Application of PACAP1-38 in Rodents.International journal of molecular sciences · 2017Article
- Nap Interferes with Hypoxia-Inducible Factors and VEGF Expression in Retina of Diabetic Rats.Journal of molecular neuroscience : MN · 2017Article
- Melatonin Represses Metastasis in Her2-Postive Human Breast Cancer Cells by Suppressing RSK2 Expression.Molecular cancer research : MCR · 2016Article
- PACAP Modulates Expression of Hypoxia-Inducible Factors in Streptozotocin-Induced Diabetic Rat Retina.Journal of molecular neuroscience : MN · 2015Article
- Investigation of the possible functions of PACAP in human trophoblast cells.Journal of molecular neuroscience : MN · 2014Article
- PACAP27 is protective against tat-induced neurotoxicity.Journal of molecular neuroscience : MN · 2014Article
- Comparative protein composition of the brains of PACAP-deficient mice using mass spectrometry-based proteomic analysis.Journal of molecular neuroscience : MN · 2014Article
- Investigation of PACAP Fragments and Related Peptides in Chronic Retinal Hypoperfusion.Journal of ophthalmology · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The integrity of retinal pigment epithelial cells is critical for photoreceptor survival and vision. Pituitary adenylate cyclase activating polypeptide (PACAP) exerts retinoprotective effects against several types of injuries in vivo, including optic nerve transection, retinal ischemia, excitotoxic injuries, UVA-induced lesion, and diabetic retinopathy. In a recent study, we have proven that PACAP is also protective in oxidative stress-induced injury in human pigment epithelial cells (ARPE-19 cells). The aim of the present study was to investigate the possible mechanisms of this protection. ARPE cells were exposed to a 24-h hydrogen peroxide treatment. Expressions of kinases and apoptotic markers were studied by complex array kits and Western blot. Oxidative stress induced the activation of several apoptotic markers, including Bad, Bax, HIF-1α, several heat shock proteins, TNF-related apoptosis-inducing ligand, and Fas-associated protein with death domain, while PACAP treatment decreased them. The changes in the expression of MAP kinases showed that PACAP activated the protective ERK1/2 and downstream CREB, and decreased the activation of the pro-apoptotic p38MAPK and c-Jun N-terminal kinase, an effect opposite to that observed with only oxidative stress. Furthermore, PACAP increased the activation of the protective Akt pathway. In addition, the effects of oxidative stress on several other signaling molecules were counteracted by PACAP treatment (Chk2, Yes, Lyn, paxillin, p53, PLC, STAT4, RSK). These play a role in cell death, cell cycle, inflammation, adhesion, differentiation and proliferation. In summary, PACAP, acting at several levels, influences the balance between pro- and anti-apoptotic factors in favor of anti-apoptosis, thereby providing protection in oxidative stress-induced injury of human retinal pigment epithelial cells.
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