Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6

Ohtaki, Hirokazu; Nakamachi, Tomoya; Dohi, Kenji; Aizawa, Yoichi; Takaki, Akira; Hodoyama, Kei; Yofu, Sachiko; Hashimoto, Hitoshi; Shintani, Norihito; Baba, Akemichi; Köpf, Manfred; Iwakura, Yoichiro; Matsuda, Kouhei; Arimura, Akira; Shioda, Seiji

doi:10.1073/pnas.0600375103

Cited by 182 publications

(204 citation statements)

References 52 publications

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“…The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) can prevent apoptosis of CGC induced by reactive oxygen species by reducing caspase-3 activity (Vaudry et al 2002). The robust neuroprotective effect of PACAP was also confirmed in vivo using various animal models of stroke (Ohtaki et al 2006;Dejda et al 2011;Lazarovici et al 2012). In neuronal lysate and living CGC, QCASP3.2 was able to detect the deleterious effect of H 2 O 2 and the protective activity of PACAP, indicating that this probe is adapted to determine caspase-3 enzymatic activity in cellular lysate as well as within cultured neurons.…”

Section: Qcasp32 Cleavage In Neurons Is Specific Of Caspase-3 Activitymentioning

confidence: 92%

Biochemical Characterization of a Caspase-3 Far-red Fluorescent Probe for Non-invasive Optical Imaging of Neuronal Apoptosis

et al. 2014

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International audienceApoptosis is a regulated process, leading to cell death, which is involved in several pathologies including neurodegenerative diseases and stroke. Caspase-3 is a key enzyme of the apoptotic pathway and is considered as a major target for the treatment of abnormal cell death. Sensitive and non-invasive methods to monitor caspase-3 activity in cells and in the brain of living animals are needed to test the efficiency of novel therapeutic strategies. In the present study, we have biochemically characterized a caspase-3 far-red fluorescent probe, QCASP3.2, that can be used to detect apoptosis in vivo. The specificity of cleavage of QCASP3.2 was demonstrated using recombinant caspases and protease inhibitors. The functionality of the probe was also established in cere-bellar neurons cultured in apoptotic conditions. QCASP3.2 did not exhibit any toxicity and appeared to accurately reflect the induction and inhibition of caspase activity by H 2 O 2 and PACAP, respectively, both in cell lysates and in cultured neurons. Finally, intravenous injection of the probe after cere-bral ischemia revealed activation of caspase-3 in the infarcted hemisphere. Thus, the present study demonstrates that QCASP3.2 is a suitable probe to monitor apoptosis both in vitro and in vivo and illustrates some of the possible applications of this caspase-3 fluorescent probe

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Section: Qcasp32 Cleavage In Neurons Is Specific Of Caspase-3 Activitymentioning

confidence: 92%

Biochemical Characterization of a Caspase-3 Far-red Fluorescent Probe for Non-invasive Optical Imaging of Neuronal Apoptosis

et al. 2014

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“…This is also true for ischemic injuries. Ohtaki and coworkers showed that PACAP KO mice have increased infarct volume in a model of stroke [ 60 ] with increased edema formation [ 61 ]. Similar results were obtained in the retina: in bilateral carotid artery occlusioninduced retinal ischemia PACAP KO mice showed increased tissue damage [ 62 ].…”

Section: Small Intestinal Ischemic Injury In Pacap Knockout (Ko) Micementioning

confidence: 59%

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

Horváth

Illés

Heimesaat

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide widely distributed throughout the body, including the gastrointestinal tract. Several effects have been described in human and animal intestines. Among others, PACAP infl uences secretion of intestinal glands, blood fl ow, and smooth muscle contraction. PACAP is a well-known cytoprotective peptide with strong anti-apoptotic, anti-infl ammatory, and antioxidant effects. The present review gives an overview of the intestinal protective actions of this neuropeptide. Exogenous PACAP treatment was protective in a rat model of small bowel autotransplantation. Radioimmunoassay (RIA) analysis of the intestinal tissue showed that endogenous PACAP levels gradually decreased with longer-lasting ischemic periods, prevented by PACAP addition. PACAP counteracted deleterious effects of ischemia on oxidative stress markers and cytokines. Another series of experiments investigated the role of endogenous PACAP in intestines in PACAP knockout (KO) mice. Warm ischemia-reperfusion injury and cold preservation models showed that the lack of PACAP caused a higher vulnerability against ischemic periods. Changes were more severe in PACAP KO mice at all examined time points. This fi nding was supported by increased levels of oxidative stress markers and decreased expression of antioxidant molecules. PACAP was proven to be protective not only in ischemic but also in infl ammatory bowel diseases. A recent study showed that PACAP treatment prolonged survival of Toxoplasma gondii infected mice suffering from acute ileitis and was able to reduce the ileal expression of proinfl ammatory cytokines. We completed the present review with recent clinical results obtained in patients suffering from infl ammatory bowel diseases. It was found that PACAP levels were altered depending on the activity, type of the disease, and antibiotic therapy, suggesting its probable role in infl ammatory events of the intestine.

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“…9). These results suggest that anti-apoptotic effects of S-memantine may be mediated by attenuation of ERK-dephosphorylation (26,27).…”

Section: Discussionmentioning

confidence: 79%

A Novel Hydrogen Sulfide-releasing N-Methyl-d-Aspartate Receptor Antagonist Prevents Ischemic Neuronal Death

Marutani

Kosugi

Tokuda

et al. 2012

Journal of Biological Chemistry

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Background:Hydrogen sulfide (H 2 S) exerts neuroprotective effects, whereas H 2 S may cause neurotoxicity via N-methyl-D-aspartate receptor (NMDAR) activation. Results: A newly-synthesized H 2 S-releasing NMDAR antagonist S-memantine exerted lower neurotoxicity and prevented ischemic neuronal death more markedly than conventional H 2 S-releasing compounds or memantine alone. Conclusion: S-memantine prevents ischemic brain injury without neurotoxicity. Significance: H 2 S-releasing NMDAR antagonists may prevent neurodegeneration of various causes.

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Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6

Cited by 182 publications

References 52 publications

Biochemical Characterization of a Caspase-3 Far-red Fluorescent Probe for Non-invasive Optical Imaging of Neuronal Apoptosis

Biochemical Characterization of a Caspase-3 Far-red Fluorescent Probe for Non-invasive Optical Imaging of Neuronal Apoptosis

Protective Intestinal Effects of Pituitary Adenylate Cyclase Activating Polypeptide

A Novel Hydrogen Sulfide-releasing N-Methyl-d-Aspartate Receptor Antagonist Prevents Ischemic Neuronal Death

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