Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals

Dóra Reglodi; Zsolt Fábián; Andrea Tamás; Andrea Lubics; József Szeberényi; Tamás Alexy; Kálmán Tóth; Zsolt Márton; Balázs Borsiczky; Erzsébet Roth; Luca Szalontay; István Lengvári

doi:10.1016/j.regpep.2004.05.012

Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals

Dóra Reglodi, Zsolt Fábián, Andrea Tamás, Andrea Lubics, József Szeberényi, Tamás Alexy, Kálmán Tóth, Zsolt Márton, Balázs Borsiczky, Erzsébet Roth, Luca Szalontay, István Lengvári

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Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) exerts neuroprotective effects in various in vitro and in vivo models of cerebral pathologies. It has been shown that PACAP protects neurons in rat models of both global and focal ischemia. In the present study, we investigated factors that may play a role in the neuroprotective effects of PACAP. PACAP strongly reduced the anisomycin-induced apoptosis of PC12 cells, which was abolished in a PKA-deficient PC12 cell line (A126). This effect was also observed in vivo, in permanent occlusion of the middle cerebral artery, where the number of TUNEL-positive neurons was significantly reduced in the ischemic core of PACAP-treated animals. Our results show that PACAP has a minor antioxidant effect in a non-cellular in vitro system, and has considerable antioxidant effects in an in vitro red blood cell filtration model. PACAP had no effect on platelet aggregation induced by collagen, ADP or epinephrine. Our results demonstrate that the effects of PACAP on delayed neuronal death may play a significant role in the reduction of the infarct size in vivo, but the antioxidant effect could only be observed at concentrations higher than that used in the model of focal ischemia.

Original language	English (US)
Pages (from-to)	51-59
Number of pages	9
Journal	Regulatory Peptides
Volume	123
Issue number	1-3 SPEC. ISS.
DOIs	https://doi.org/10.1016/j.regpep.2004.05.012
State	Published - Dec 15 2004
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by the National Science Research Fund (OTKA T034491 046589 and T037528), the Hungarian Ministry of Health (ETT 596/2003 and ETT 073/2001), the Hungarian Academy of Sciences and Bolyai Scholarship. The authors thank Brian K. Lucas for critically reviewing the manuscript.

Keywords

Antioxidant
Middle cerebral artery
Permanent focal ischemia
Protein kinase A
Red blood cell filtration

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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Reglodi, D., Fábián, Z., Tamás, A., Lubics, A., Szeberényi, J., Alexy, T., Tóth, K., Márton, Z., Borsiczky, B., Roth, E., Szalontay, L., & Lengvári, I. (2004). Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals. Regulatory Peptides, 123(1-3 SPEC. ISS.), 51-59. https://doi.org/10.1016/j.regpep.2004.05.012

Reglodi, D, Fábián, Z, Tamás, A, Lubics, A, Szeberényi, J, Alexy, T, Tóth, K, Márton, Z, Borsiczky, B, Roth, E, Szalontay, L & Lengvári, I 2004, 'Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals', Regulatory Peptides, vol. 123, no. 1-3 SPEC. ISS., pp. 51-59. https://doi.org/10.1016/j.regpep.2004.05.012

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abstract = "Pituitary adenylate cyclase activating polypeptide (PACAP) exerts neuroprotective effects in various in vitro and in vivo models of cerebral pathologies. It has been shown that PACAP protects neurons in rat models of both global and focal ischemia. In the present study, we investigated factors that may play a role in the neuroprotective effects of PACAP. PACAP strongly reduced the anisomycin-induced apoptosis of PC12 cells, which was abolished in a PKA-deficient PC12 cell line (A126). This effect was also observed in vivo, in permanent occlusion of the middle cerebral artery, where the number of TUNEL-positive neurons was significantly reduced in the ischemic core of PACAP-treated animals. Our results show that PACAP has a minor antioxidant effect in a non-cellular in vitro system, and has considerable antioxidant effects in an in vitro red blood cell filtration model. PACAP had no effect on platelet aggregation induced by collagen, ADP or epinephrine. Our results demonstrate that the effects of PACAP on delayed neuronal death may play a significant role in the reduction of the infarct size in vivo, but the antioxidant effect could only be observed at concentrations higher than that used in the model of focal ischemia.",

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AU - Reglodi, Dóra

AU - Fábián, Zsolt

AU - Tamás, Andrea

AU - Lubics, Andrea

AU - Szeberényi, József

AU - Alexy, Tamás

AU - Tóth, Kálmán

AU - Márton, Zsolt

AU - Borsiczky, Balázs

AU - Roth, Erzsébet

AU - Szalontay, Luca

AU - Lengvári, István

N1 - Funding Information: This work was supported by the National Science Research Fund (OTKA T034491 046589 and T037528), the Hungarian Ministry of Health (ETT 596/2003 and ETT 073/2001), the Hungarian Academy of Sciences and Bolyai Scholarship. The authors thank Brian K. Lucas for critically reviewing the manuscript.

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N2 - Pituitary adenylate cyclase activating polypeptide (PACAP) exerts neuroprotective effects in various in vitro and in vivo models of cerebral pathologies. It has been shown that PACAP protects neurons in rat models of both global and focal ischemia. In the present study, we investigated factors that may play a role in the neuroprotective effects of PACAP. PACAP strongly reduced the anisomycin-induced apoptosis of PC12 cells, which was abolished in a PKA-deficient PC12 cell line (A126). This effect was also observed in vivo, in permanent occlusion of the middle cerebral artery, where the number of TUNEL-positive neurons was significantly reduced in the ischemic core of PACAP-treated animals. Our results show that PACAP has a minor antioxidant effect in a non-cellular in vitro system, and has considerable antioxidant effects in an in vitro red blood cell filtration model. PACAP had no effect on platelet aggregation induced by collagen, ADP or epinephrine. Our results demonstrate that the effects of PACAP on delayed neuronal death may play a significant role in the reduction of the infarct size in vivo, but the antioxidant effect could only be observed at concentrations higher than that used in the model of focal ischemia.

AB - Pituitary adenylate cyclase activating polypeptide (PACAP) exerts neuroprotective effects in various in vitro and in vivo models of cerebral pathologies. It has been shown that PACAP protects neurons in rat models of both global and focal ischemia. In the present study, we investigated factors that may play a role in the neuroprotective effects of PACAP. PACAP strongly reduced the anisomycin-induced apoptosis of PC12 cells, which was abolished in a PKA-deficient PC12 cell line (A126). This effect was also observed in vivo, in permanent occlusion of the middle cerebral artery, where the number of TUNEL-positive neurons was significantly reduced in the ischemic core of PACAP-treated animals. Our results show that PACAP has a minor antioxidant effect in a non-cellular in vitro system, and has considerable antioxidant effects in an in vitro red blood cell filtration model. PACAP had no effect on platelet aggregation induced by collagen, ADP or epinephrine. Our results demonstrate that the effects of PACAP on delayed neuronal death may play a significant role in the reduction of the infarct size in vivo, but the antioxidant effect could only be observed at concentrations higher than that used in the model of focal ischemia.

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KW - Permanent focal ischemia

KW - Protein kinase A

KW - Red blood cell filtration

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ER -

Effects of PACAP on in vitro and in vivo neuronal cell death, platelet aggregation, and production of reactive oxygen radicals

Abstract

Bibliographical note

Keywords

UN SDGs

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