PACAP-derived mutant peptide MPAPO protects trigeminal ganglion cell and the retina from hypoxic injury through anti-oxidative stress, anti-apoptosis, and promoting axon regeneration

Li, Huixian; Feng, Jia; Liu, Qian; Ou, Biqian; Lu, Shiyin; Ma, Yi

doi:10.1016/j.bbagen.2021.130018

Cited by 3 publications

(1 citation statement)

References 91 publications

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“…MPAPO, a highly stable PACAP-27-derived mutant peptide, and PACAP were proven to mitigate apoptosis evoked by hypoxic conditions in trigeminal ganglion cells. Both peptides decreased caspase-3 activity and cytochrome c release [63]. PACAP was shown to prevent rat schwannoma cells from apoptosis induced by serum deprivation by influencing components of the apoptotic signaling cascade.…”

Section: Effects Of Pacap On Cell Death In the Peripheral Nervous Systemmentioning

confidence: 85%

Effects of Pituitary Adenylate Cyclase Activating Polypeptide on Cell Death

Horváth

Reglődi

Fábián

et al. 2022

IJMS

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Pituitary adenylate cyclase activating polypeptide (PACAP) was first isolated as a hypothalamic peptide based on its efficacy to increase adenylate cyclase (AC) activity. It has a widespread distribution throughout the body including the nervous system and peripheral organs, where PACAP exerts protective effects both in vivo and in vitro through its anti-apoptotic, anti-inflammatory, and antioxidant functions. The aim of the present paper was to review the currently available literature regarding the effects of PACAP on cell death in vitro in neural and non-neural cells. Among others, its effect on apoptosis can be detected in cerebellar granule cells against different toxic stimuli. Different neural cell types from the cerebral cortex are also prevented from cell death. PACAP also shows effects on cell death in cells belonging to the peripheral nervous system and protects both neural and non-neural cells of sensory organs. In addition, cell survival-promoting effect can be observed in different peripheral organ systems including cardiovascular, immune, respiratory, gastrointestinal, urinary, and reproductive systems. The studies summarized here indicate its noteworthy effect on cell death in different in vitro models, suggesting PACAP’s potential therapeutic usage in several pathological conditions.

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Section: Effects Of Pacap On Cell Death In the Peripheral Nervous Systemmentioning

confidence: 85%

Effects of Pituitary Adenylate Cyclase Activating Polypeptide on Cell Death

Horváth

Reglődi

Fábián

et al. 2022

IJMS

View full text Add to dashboard Cite

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Exploring the response of PACAP on thermal endurance of F-actin by differential scanning calorimetry

Bukovics,

Lőrinczy

2024

J Therm Anal Calorim

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Pituitary adenylate cyclase-activating polypeptide (PACAP) is a bioactive peptide known for its diverse effects on the nervous system. While numerous studies have demonstrated the neuroprotective properties of PACAP, its role in tissue regeneration and potential as a therapeutic agent remain to be fully understood. Specifically, the understanding of PACAP’s impact on cytoskeletal dynamics, particularly the organization and disorganization of actin filament networks, is limited due to the scarcity of in vitro studies in this area. Additionally, the interaction between PACAP and actin has been minimally explored, and the influence of PACAP on the thermal stability of actin is completely unknown. To address these gaps, the current study aimed to investigate the impact of different forms and fragments of PACAP on the thermal denaturation and renaturation of Ca2+-F-actin using a differential scanning calorimetry (DSC) approach. Our primary objective was to determine whether PACAP modulates the thermal stability of Ca2+-F-actin and establish a temperature-dependent pattern of any structural alterations that may occur as a result of PACAP interaction. Two PACAP forms exist in vivo: the 38 amino acid length PACAP38 and the PACAP27, the latter truncated at the C-terminal. Both in the PACAP38 + Ca2+-F-actin and in the PACAP6-38 + Ca2+-F-actin mixtures, the DSC scans exhibited a significant decrease of actin denaturation temperature compared to the control; however, the PACAP27 + Ca2+-F-actin and PACAP6-27 + Ca2+-F-actin revealed no remarkable differences compared to the actin control sample. The calorimetric enthalpy of the truncated PACAP27 and PACAP6-27 + actin mixture also followed the tendencies mentioned above. Thus, in PACAP27 and PACAP6-27 mixture, there was no change in the denaturation temperature of actin, and no significant ΔHcal was observed. Through this research, we sought to elucidate the underlying mechanisms of PACAP’s effects on actin dynamics using thermal de- and renaturation cycles.

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Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina: Microglial Activation and Induction of Neural Proliferation

Denes,

Lukats,

Szarka

et al. 2023

Neurochem Res

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The degenerative retinal disorders characterized by progressive cell death and exacerbating inflammation lead ultimately to blindness. The ubiquitous neuropeptide, PACAP38 is a promising therapeutic agent as its proliferative potential and suppressive effect on microglia might enable cell replacement and attenuate inflammation, respectively. Our previous finding that PACAP38 caused a marked increase of the amacrine cells in the adult (1-year-old) mouse retina, served as a rationale of the current study. We aimed to determine the proliferating elements and the inflammatory status of the PACAP38-treated retina. Three months old mice were intravitreally injected with 100 pmol PACAP38 at 3 months intervals (3X). Retinas of 1-year-old animals were dissected and effects on cell proliferation, and expression of inflammatory regulators were analyzed. Interestingly, both mitogenic and anti-mitogenic actions were detected after PACAP38-treatment. Further analysis of the mitogenic effect revealed that proliferating cells include microglia, endothelial cells, and neurons of the ganglion cell layer but not amacrine cells. Furthermore, PACAP38 stimulated retinal microglia to polarize dominantly into M2-phenotype but also might cause subsequent angiogenesis. According to our results, PACAP38 might dampen pro-inflammatory responses and help tissue repair by reprogramming microglia into an M2 phenotype, nonetheless, with angiogenesis as a warning side effect.

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PACAP-derived mutant peptide MPAPO protects trigeminal ganglion cell and the retina from hypoxic injury through anti-oxidative stress, anti-apoptosis, and promoting axon regeneration

Cited by 3 publications

References 91 publications

Effects of Pituitary Adenylate Cyclase Activating Polypeptide on Cell Death

Effects of Pituitary Adenylate Cyclase Activating Polypeptide on Cell Death

Exploring the response of PACAP on thermal endurance of F-actin by differential scanning calorimetry

Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina: Microglial Activation and Induction of Neural Proliferation

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