Apelin-36, a potent peptide, protects against ischemic brain injury by activating the PI3K/Akt pathway

Gu, Qing; Zhai, Lijing; Feng, Xing; Chen, Jing; Miao, Zhigang; Ren, Liyan; Qian, Xuanchen; Yu, Jian; Li, Yan; Xu, Xingshun; Liu, Chunfeng

doi:10.1016/j.neuint.2013.09.017

Cited by 68 publications

(47 citation statements)

References 35 publications

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“…The mechanisms responsible for the protective effects of apelin-36 against H/I brain injury involved a decrease in the levels of cleaved caspase-3 and Bax. Apelin-36 also increased the expression level of phosphorylated Akt; however, with the use of a specific PI3K inhibitor, the levels of phosphorylated Akt decreased, and the protective effects of apelin-36 against apoptosis were attenuated (72). This suggests that the PI3K/Akt pathway is at least partly involved in the anti-apoptotic effects of apelin-36.…”

Section: Apelin Protects the Central Nervous System By Stimulating Romentioning

confidence: 98%

“…The apelin/APJ system has a number of biological functions; for instance, apelin has been shown to exert cardioprotective effects in renal ischemia-reperfusion injury (105). In cerebral ischemia-reperfusion, both apelin-13 and apelin-36 can protect neurons and inhibit damage induced by inflammation by activating the PI3K/Akt pathway (72,106,107). Furthermore, small molecular compounds may be developed to target the apelin/APJ system for the treatment of inflammationrelated diseases.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

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Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

Zhou

Cao

Chen

2016

International Journal of Molecular Medicine

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Abstract. Apelin, the endogenous ligand of APJ which is a member of G protein-coupled receptors, has been shown to be expressed in a variety of tissues in vivo and to exert significant biological effects. Studies have indicated that the apelin/APJ system is involved in the regulation of a variety of physiological functions and pathological processes, and that it is associated with cardiovascular diseases (such as atherosclerosis, hypertension, heart failure and myocardial injury), diabetes with microvascular complications, ischemia reperfusion injury, tumors, pre-eclampsia, as well as others. The occurrence of these diseases is closely related to endothelial dysfunction and the local inflammatory response; however, the occurrence of oxidative stress is related to vascular injury, due to the excessive generation of reactive oxygen species (ROS) and can lead to vascular damage and a series of inflammatory reactions. Therefore, this review summarizes the association between apelin/APJ, oxidative stress and inflammation-related diseases. In addition, drugs targeting the apelin/APJ system are recommended, thus providing a novel therapeutic strategy for oxidative stress-related inflammatory diseases.

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Section: Apelin Protects the Central Nervous System By Stimulating Romentioning

confidence: 98%

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

Zhou

Cao

Chen

2016

International Journal of Molecular Medicine

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“…Furthermore, apelin suppresses serum deprivation-induced apoptosis of human VSMCs [102] and of rat bone marrow-derived mesenchymal stem cells [103], the latter bearing great promise for ischemic tissue repair, despite their poor viability within ischemic tissues. Of interest, the apelin/APJ system has positive effects on the apoptotic potential in organs other than the cardiovascular system [104][105][106][107][108], further supporting the beneficial systemic effects of this drug.…”

Section: Protection Against Apoptosismentioning

confidence: 99%

Effects of apelin on the cardiovascular system

et al. 2015

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Apelin is an endogenous peptide acting on the APJ receptor. It consists of several isoforms characterised by different numbers of aminoacids. The number of aminoacids in the active isoforms range from 36 to 12. Apelin-13 and, to a lesser extent, apelin-36 are considered the most active isoforms with the greatest activity on the cardiovascular homeostasis. The effects normally exerted by the basal level of endogenous apelin, can be enhanced not only by its up-regulation, but may also by its exogenous administration. The present review considers the effects of apelin on various aspects of the cardiovascular function, such as cardiac development, vasomotor tone, angiogenesis, myocardial inotropy in healthy and failing hearts as well as the prevention of ischemia-reperfusion injury, cardiac fibrosis and remodeling. Also the biphasic changes of apelin level during the evolution of heart failure are considered. Although the positive inotropic effect exerted by apelin in normal and failing hearts would suggest the use of this peptide in the treatment of heart failure, the limited duration and extent of its effect do not support this possibility, unless a long lasting (6 hours) infusion is performed to overcome the limit of its short life. However, although the data on the characteristics of the inotropic activity do not provide a strong support for the treatment of active heart failure, apelin may be used in the prevention of heart failure because of its activity in limiting the consequences of myocardial ischemia such as infarct size and cardiac remodeling. KeywordsApelin/APJ system, heart failure, ischemia-reperfusion injury, contractility, cardiac protection, Reninangiotensin system 2 The apelin/APJ system Apelin In 1998 Tatemoto et al. discovered the endogenous peptide capable of binding the G protein-coupled receptor (GPCR) APJ [1,2], which at that time was considered an orphan receptor becaue its ligand was unknown. The just discovered ligand was called, apelin e.g APj Endogenous LIgaNd. Apelin is expressed in hearts, lungs, kidneys, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma. The gene of apelin is located on chromosome X [3] and encodes a 77 aminoacid sequence called pre-pro-apelin [4]. Upon cleavage by a family of endopeptidases, pre-pro-apelin generates several C-terminal fragments of various size, which are classified on the basis of the number of aminoacids. The active isoforms range from 36 to 12 aminoacids. As fragments shorter than 12 aminoacids are biologically inactive, it appears evident that the Cterminal 12 aminoacids are essential for receptor binding, whereas the N-terminal sequence modulates the interaction with the receptor [5]. At present it is recognized that, although different isoforms display similar functions, active isoforms differ in tissue distribution, potency and receptor binding affinity [6]. Apelin-13 and, to a lesser extent, apelin-36 have been considered the most active isoforms with the greatest activity on the cardi...

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“…ACCEPTED MANUSCRIPT 8 injury through the activation of PI3K/Akt transduction pathway [63] . In brief, the apelin/APJ system serves as a potential target for the prevention of ischemic HF and ischemic brain injury.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Apelin/APJ signaling in hypoxia-related diseases

Chen

2015

Clinica Chimica Acta

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Apelin-36, a potent peptide, protects against ischemic brain injury by activating the PI3K/Akt pathway

Cited by 68 publications

References 35 publications

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review)

Effects of apelin on the cardiovascular system

Apelin/APJ signaling in hypoxia-related diseases

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