Pituitary adenylate cyclase-activating polypeptide protects astroglial cells against oxidative stress-induced apoptosis: PACAP prevents H2O2-induced astrocyte cell death
Open accessAbstract
Oxidative stress, associated with a variety of disorders including neurodegenerative diseases, results from accumulation of reactive oxygen species (ROS). Oxidative stress is not only responsible for neuron apoptosis, but can also provoke astroglial cell death. Numerous studies indicate that pituitary adenylate cyclase-activating polypeptide (PACAP) promotes neuron survival, but nothing is known regarding the action of PACAP on astroglial cell survival. Thus, the purpose of the present study was to investigate the potential glioprotective effect of PACAP on H(2)O(2)-induced astrocyte death. Pre-treatment of cultured rat astrocytes with nanomolar concentrations of PACAP prevented cell death provoked by H(2)O(2) (300 μM), whereas vasoactive intestinal polypeptide was devoid of protective activity. The effect of PACAP on astroglial cell survival was abolished by the type 1 PACAP receptor antagonist, PACAP6-38. The protective action of PACAP was blocked by the protein kinase A inhibitor H89, the protein kinase C inhibitor chelerythrine and the mitogen-activated protein (MAP)-kinase kinase (MEK) inhibitor U0126. PACAP stimulated glutathione formation, and blocked H(2)O(2)-evoked ROS accumulation and glutathione content reduction. In addition, PACAP prevented the decrease of mitochondrial activity and caspase 3 activation induced by H(2)O(2). Taken together, these data indicate for the first time that PACAP, acting through type 1 PACAP receptor, exerts a potent protective effect against oxidative stress-induced astrocyte death. The anti-apoptotic activity of PACAP on astrocytes is mediated through the protein kinase A, protein kinase C and MAPK transduction pathways, and can be accounted for by inhibition of ROS-induced mitochondrial dysfunctions and caspase 3 activation.
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The PACAP/PAC1 pathway is involved in an oxidative stress protective system against ROS-induced mitochondrial dysfunctions and apoptosis.
“Moreover, this pathway seems to be involved also in an oxidative stress protective system against ROS-induced mitochondrial dysfunctions and apoptosis [198].”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [198]
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Balmus, I. M., Ciobica, A., Antioch, I., Dobrin, R., & Timofte, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3975101 · Cited by 103 · see citing works
“Moreover, this pathway seems to be involved also in an oxidative stress protective system against ROS-induced mitochondrial dysfunctions and apoptosis [198].”
Background
- Authors
- Masmoudi-Kouki, O., Douiri, S., Hamdi, Y., Kaddour, H., Bahdoudi, S., Vaudry, D., Basille, M., Leprince, J., Fournier, A., Vaudry, H., Tonon, M.-C., & Amri, M.
- Affiliations
- Tunis University (TN)
- Inserm (FR)
- Institut National de la Recherche Scientifique (CA)
- Corresponding author
- Vaudry, Hubert
- Amri, Mohamed
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2011-03-15
- Volume
- 117
- Issue
- 3
- Pages
- 403-411
- ISSN
- 0022-3042 (ISSN-L)
- OpenAlex
- W1490818157
- Cited by
- 66
- References
- 47
- Citations by year
- 2025: 3 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 6 · 2018: 10 · 2017: 3 · 2016: 12 · 2015: 4 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Université de Tunis
- Université de Tunis El Manar
- Région Normandie
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Pharmacology › Apelin-related biomedical research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- pituitary adenylate cyclase-activating polypeptide, PACAP, astrocytes, oxidative stress, apoptosis, hydrogen peroxide, reactive oxygen species, glutathione, protein kinase A, protein kinase C, MAPK signaling, caspase-3, mitochondrial dysfunction, neuroprotection
- MeSH terms
- Animals, Animals, Newborn, Astrocytes, Cells, Cultured, Cerebellum, Cerebral Cortex, Drug Interactions, Glutathione, Hydrogen Peroxide, Mitochondria, Neurons, Signal Transduction, Culture Media, Conditioned, Rats, Wistar, Apoptosis, Reactive Oxygen Species, Oxidative Stress, Pituitary Adenylate Cyclase-Activating Polypeptide, Rats, Caspase 3
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