Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation

Qing, Xin; Cheng, Baohua; Pan, Yanyou; Liu, Haiqing; Yang, Chunqing; Chen, Jing; Bai, Bo

doi:10.1016/j.peptides.2014.09.016

Cited by 112 publications

(78 citation statements)

References 36 publications

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“…Recent studies showed that Apelin had the neuroprotective effect. Xin et al [28] revealed that Apelin-13 was neuroprotective for neurons against cerebral ischemia/reperfusion through inhibiting the neuroinflammation. Zeng et al [29] found that Apelin was an endogenous neuroprotective adipocytokine that might block apoptosis and excitotoxic death via cellular and molecular mechanisms.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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Organophosphate-induced delayed neuropathy (OPIDN) is pathologically characterized by the swollen axon containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles. At present, the exact mechanism of OPIDN is unclear and the effective therapeutic methods is not available to counter this syndrome. Recent studies had shown that the autophagy was involved in OPIDN. The adipocytokine Apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous system. Recent researches illuminated that Apelin was neuroprotective factor and Apelin could regulate the autophagy in vivo and vitro model. So we investigated the effect of Apelin-13 on the OPIDN induced by Tri-ortho-cresyl phosphate (TOCP) in hens and explored the role of autophagy in Apelin-13 preventing OPIDN. Adult Roman hens were given a single dose of 750 mg/kg TOCP by gavage for 21 days to induce OPIDN, and neural dysfunction were detected, and the formation of autophagosomes in spinal cord neurons was observed by transmission electron microscopy, and the molecular markers of autophagy microtubule-associated protein light chain-3 (LC3) and the autophagy substrates p62/SQSTM1 were determined by Western blot analysis. The results demonstrated that the obvious neurological dysfunction such as hindlimb paralysis and paralysis of gait was present, the number of autophagosomes in the neurons of spinal cords was significantly increased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly increased in the OPIDN model group compared with the control group. Compared with the OPIDN model group, the neurological dysfunction of tens was obviously reduced, the clinical signs scores was significantly decreased, the number of autophagosomes in the neurons of hen spinal cords was significantly decreased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly decreased in Apelin-13 treatment group. Our results suggested that Apelin-13 prevented against the OPIDN induced by TOCP in hens, which the mechanism might be associated with regulation autophagy flux by Apelin-13.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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“…It has been reported that Apelin-13 protects against cerebral ischemia by reducing infarct volume and brain edema as well as inhibiting apoptosis and inflammation [3,4,22]. As known to us, BBB is composed of endothelial cells, tight junctions, astrocyte end-feet and pericytes, maintaining homeostasis of the neuro-parenchymal microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…Apelin-13 is one of the most active forms of Apelin and has a number of biological effects. Several studies have demonstrated its neuroprotective effects on cerebral ischemic models, including apoptosis reduction and inflammation inhibition [3,4]. However, the involved mechanisms remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Apelin-13 Protects against Ischemic Blood-Brain Barrier Damage through the Effects of Aquaporin-4

et al. 2017

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Background: Apelin-13 has been found to have protective effects on many neurological diseases, including cerebral ischemia. However, whether Apelin-13 acts on blood-brain barrier (BBB) disruption following cerebral ischemia is largely unknown. Aquaporin-4 (AQP4) has a close link with BBB due to the high concentration in astrocyte foot processes and regulation of astrocytes function. Here, we aimed to test Apelin-13′s effects on ischemic BBB injury and examine whether the effects were dependent on AQP4. Methods: We detected the expression of AQP4 induced by Apelin-13 injection at 1, 3, and 7 days after middle cerebral artery occlusion. Meanwhile, we examined the effects of Apelin-13 on neurological function, infarct volume, and BBB disruption owing to cerebral ischemia in wild type mice, and tested whether such effects were AQP4 dependent by using AQP4 knock-out mice. Furthermore, we assessed the possible signal transduction pathways activated by Apelin-13 to regulate AQP4 expression via astrocyte cultures. Results: It was found that Apelin-13 highly increased AQP4 expression as well as reduced neurological scores and infarct volume. Importantly, Apelin-13 played a role of BBB protection in both types of mice by reducing BBB permeability, increased vascular endothelial growth factor, upregulated endothelial nitric oxide synthase, and downregulated inducible NOS. In morphology, we demonstrated Apelin-13 suppressed tight junction opening and endothelial cell swelling via electron microscopy detection. Meanwhile, Apelin-13 also alleviated apoptosis of astrocytes and promoted angiogenesis. Interestingly, effects of AQP4 on neurological function and infarct volume varied with time course, while AQP4 elicited protective effects on BBB at all time points. Statistical analysis of 2-way analysis of variance with replication indicated that AQP4 was required for these effects. In addition, Apelin-13 upregulated phosphorylation of extracellular signal-regulated kinase (ERK) and Akt as well as AQP4 protein in cultured astrocytes. The latter was inhibited by ERK and phosphatidylinositol 3′-kinase (PI3K) inhibitors. Conclusion: Our data suggest that Apelin-13 protects BBB from disruption after cerebral ischemia both morphologically and functionally, which is highly associated with the increased levels of AQP4, possibly through the activation of ERK and PI3K/Akt pathways. This study provides double targets to protection of ischemic BBB damage, which can present new insights to drugs development.

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“…Although no drugs targeting HMGB-1 were used in clinical practice, some anti-HMGB-1 agents were shown to inhibit the expression of HMGB-1 in ischemic animal models, including glycyrrhizin [90,149,150], ethyl pyruvate (EP) [151,152], tanshinone IIA [153,154], fluvastatin [155], berberine [156], moclobemide [157], minocycline [158], probenecid [159], portulaca [160], apelin-13 [161], hesperidin [162] and bleacein [163]. Glycyrrhizin, a glycoconjugated triterpene present in licorice root, has been shown to exert protective effects in various diseases via suppressing HMGB-1.…”

Section: Therapeutic Strategy For Hmgb-1mentioning

confidence: 99%

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

Pei

et al. 2018

Cell Physiol Biochem

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High mobility group box-1 (HMGB-1), a typical damage-associated molecular pattern protein released from various cells, was first identified in 1973. It is usually stored in the nuclei of cells. Several modifications of HMGB-1 promote its translocation to the cytosol, and it is actively or passively released from cells. When outside of the cells, HMGB-1is crucial in inflammation. It exerts its biological functions via interaction with its receptors, including receptor for advanced glycation end products (RAGE) and Toll-like receptor 4(TLR4). A large number of studies showed a close link between inflammation and thrombosis. This review demonstrated the increased expression of HMGB-1 in thrombosis-related diseases, including coronary artery disease, stroke, peripheral arterial disease, disseminated intravascular coagulation, and venous thrombosis. Besides, it summarized the current understanding of the emerging link between HMGB-1 and thrombosis from three aspects: platelet, NETs, and coagulation and fibrinolysis factors. Finally, it explored the possible therapeutic strategies targeting HMGB-1 for treating thrombosis-related diseases.

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Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation

Cited by 112 publications

References 36 publications

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

Apelin-13 Protects against Ischemic Blood-Brain Barrier Damage through the Effects of Aquaporin-4

Emerging Role of High Mobility Group Box-1 in Thrombosis-Related Diseases

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