通讯机构：
[Li, LF; Chen, LX] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
The P2X7 receptor;Myocardial ischemia-reperfusion injury;Dilated cardiomyopathy;Autoimmune myocarditis;Atherosclerosis;Diabetic retinopathy
摘要：
The P2X7 purinergic receptor, a calcium permeable cationic channel, is activated by extracellular ATP. Most studies show that P2X7 receptor plays an important role in the nervous system diseases, immune response, osteoporosis and cancer. Mounting evidence indicates that P2X7 receptor is also associated with cardiovascular disease. For example, the P2X7 receptor activated by ATP can attenuate myocardial ischemia-reperfusion injury. By contrast, inhibition of P2X7 receptor decreases arrhythmia after myocardial infarction, prolongs cardiac survival after a long term heart transplant, alleviates the dilated cardiomyopathy and the autoimmune myocarditis process. The P2X7 receptor also mitigates vascular diseases including atherosclerosis, hypertension, thrombosis and diabetic retinopathy. This review focuses on the latest research on the role and therapeutic potential of P2X7 receptor in cardiovascular diseases.
作者机构：
[Tang M.; Luo X.; Huang Z.; Chen L.] Learning Key Laboratory for Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China
通讯机构：
[Zhen Huang; Linxi Chen] L;Learning Key Laboratory for Pharmacoproteomics, Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
关键词：
mitochondrial proteins;stress;mitochondria
摘要：
Mitochondria are dynamic, double-membrane-bound organelle of eukaryotic cells that have evolved to function in a wide range of cellular processes. They are responsible for oxidative phosphorylation (OXPHOS), producing energy and metabolites, regulating apoptosis and maintaining cell viability. To properly perform these functions, mitochondria depend on hundreds of proteins which are encoded in the nucleus, synthesized in the cytosol, and imported into the organelle. The transport of mitochondrial preproteins is mainly mediated by the translocase of the outer mitochondrial membrane and the translocase of the inner mitochondrial membrane [1]. Given the dependence of mitochondrial function on cytosolic synthesized proteins, maintaining efficient mitochondrial protein import is indispensable for cellular and organismal health. Therefore, it is not surprising that some sophisticated protective responses must exist to defend against deficient mitochondrial protein import in cells.
作者：
Qionglin Zhou;Kai Zhang;Yu Guo;Linxi Chen;Lanfang Li
期刊：
生物化学与生物物理学报,2018年50(3):319-321 ISSN：1672-9145
通讯作者：
Linxi Chen<&wdkj&>Lanfang Li
作者机构：
[Zhou Qionglin; Zhang Kai; Guo Yu; Chen Linxi; Li Lanfang] Institute of Pharmacy and Pharmacology, University of South China, Learning Key Laboratory for Pharmacoproteomics;[Zhou Qionglin; Zhang Kai; Guo Yu; Chen Linxi; Li Lanfang] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001
通讯机构：
[Linxi Chen; Lanfang Li] I
关键词：
pregnancy;embryologic development
摘要：
APJ is a seven-transmembrane G protein coupled receptor. Apelin is an endogenous ligand of APJ [1]. It is well known that Apelin and APJ receptor are widely distributed in a variety of organs including the heart, brain, kidney, stomach, lung, adipose tissues, endothelium, vascular smooth muscle cells, testis, ovary, and gland, particularly in the cardiovascular system. The Apelin/APJ system plays multiple important roles in various physiological and pathological processes such as regulation of blood pressure, cardiac contractility, water homeostasis, immunity, glucose metabolism, fat metabolism, inflammation, liver fibrosis, cardiovascular development, apoptosis, revascularization, as well as cell proliferation.
作者机构：
[CHEN Zhe; HUANG Zhen; CHEN Lin Xi] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, Hunan, China
通讯机构：
[HUANG, Z.] I;Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan, China
关键词：
嗅觉;受体;治疗学;疾病;神经原;醋酸;基因;果蝇
摘要：
Recently, Prieto-Godino et al. found that the olfactory receptor 75a (Ir75a) gene is a functional pseudo-pseudogene in Drosophila sechellio. For a long time, Ir75a has been regarded as an acetic acid receptor that detects acetic acid and induces obvious olfactory responses in olfactory sensory neurons (OSNs). Nonetheless, Prieto-Godino et al. confirmed that Ir75a lost its sensitivity to acetic acid in D. sechellia. Thus, the D. sechellia lr75a gene is generally recognized as a pseudogene in OSNs. Nevertheless, the D. sechellia Ir75a gene is not a simple pseudogene. Prieto-Godino et al. found that D. sechellia Ir75a is sensitive to propionic, butyric, and 2-oxopentanoic acids. Therefore, the D. sechellia Ir75a gene encodes a functional olfactory receptor (OR) that induces different olfactory responses.
摘要：
Apelin, an endogenous ligand for the G protein-coupled receptor APJ, is widely expressed in various organs. Recent research has indicated that the Apelin/APJ system plays an important role in aging. Apelin and APJ receptor expression are down-regulated with increasing age. In murine models, Apelin and APJ knockouts exhibit accelerated senescence whereas Apelin-restoration results in enhanced vigor and rejuvenated behavioral and circadian phenotypes. Furthermore, aged Apelin knockout mice develop progressive impairment of cardiac contractility associated with systolic dysfunction. Apelin is crucial to maintain cardiac contractility in aging. Moreover, the Apelin/APJ system appears to be involved in regulation of renin-angiotensin-aldosterone system (RAAS), apoptosis, inflammation and oxidative stress which promotes aging. Likewise, the Apelin/APJ system regulates autophagy, stem cells and the sirtuin family thus contributing to anti-aging. In this review, we describe the relationship between Apelin/APJ system and aging. We elaborate on the role of the Apelin/APJ system in aging stimulators, aging inhibitors and age-related diseases such as obesity, diabetes and cardiovascular disease. We conclude that Apelin/APJ system might become a novel promising therapeutic target for anti-aging.
摘要：
Retracted article: Nucleophagy in Human Disease: Beyond the Physiological Role. [Tohoku J. Exp. Med., 2018, 244 (1), 75-81. doi: 10.1620/tjem.244.75.]
The above article was published online on January 27, 2018. Soon after its publication (on February 1, 2018), Dr. Nian Fu and Prof. Linxi Chen informed the Editor-in-Chief, () about serious violation of publication ethics. Indeed, Dr. Nian Fu and Prof. Linxi Chen were astonished to find their names as coauthors of this article, because they were not involved in the submission process of this article and they do not know any of other coauthors. In addition, the article is similar to their unpublished manuscript.
After a thorough investigation in accordance with the recommendations of the Committee on Publication Ethics (COPE), the Editor-in-Chief of decided to retract this article. The reasons for Retraction are summarized below: forged authors and an unexpected case of plagiarism.
: Dr. Nian Fu and Prof. Linxi Chen were added as co-authors of the article without their knowledge. In fact, the signature provided by Prof. Linxi Chen is apparently different from the signature of a coauthor, named on the AUTHORS’ RESPONSIBILITY FORM, provided by the corresponding author of the article. More critically, the signature provided by Dr. Nian Fu is completely different from the signature of , because the Chinese characters are different between the two signatures. In addition, the replies from three authors (Ming Zhou, Hongwen Ji and Yong Xia) clearly indicate that they misunderstand the identity of Dr. Nina Fu. We also attempted to contact two authors, named and , via e-mail. As expected, the forged authors did not respond to our inquiries, despite that their e-mail addresses appear to be active.
: This article is similar to the unpublished manuscript prepared by Dr. Nian Fu and Prof. Linxi Chen. Moreover, two figures used in the article are identical to the preliminary figures of their unpublished manuscript. According to Dr. Nian Fu, a local agency for language editing had transferred their unpublished manuscript to a third party. Unfortunately, the check system of is not effective for plagiarism of unpublished materials. We believe that the corresponding author of the article included the names of the original two authors to avoid the criticism of plagiarism. Eventually, the corresponding author agreed to retract the article.
We apologize for any inconvenience caused by this retraction to readers. We also hope that the publication of the plagiarized article will not trouble Dr. Nian Fu and Prof. Linxi Chen too much.
期刊：
CURRENT DRUG TARGETS,2018年19(15):1767-1773 ISSN：1389-4501
通讯作者：
Chen, Linxi
作者机构：
[Fu, Nian; Yang, XueFeng] Univ South China, Affiliated Nanhua Hosp, Dept Gastroenterol, Hengyang, Hunan, Peoples R China.;[Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang, Hunan, Peoples R China.;[Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.
通讯机构：
[Chen, Linxi] U;Univ South China, Inst Pharm & Pharmacol, Hengyang, Peoples R China.
关键词：
Nucleophagy;nuclear lamina;microtubule-associated protein 1 light chain 3(LC3);autophagy-related genes (Atg);autophagy;parakeratosis and psoriasis.
摘要：
Nucleophagy is a selective autophagy, which selectively removes damaged or non-essential nuclear material from a cell by the autophagy pathway. Additionally, nucleophagy is crucial for promoting cell longevity and ensure body proper function. Increasing evidence has shown that nucleophagy may play a major role in such human diseases as degenerative disorders, tumorigenesis, malnutrition and metabolic disorders, parakeratosis and psoriasis. Studies indicated that nucleophagy can improve degenerative disorders by delaying premature cell senescence, prevent malnutrition and metabolic disorder via maintaining nuclear structure and releasing nutrients for energy production, and alleviate parakeratosis and psoriasis. But the activation of nucleophagy appears to be a double-edged sword. Some studies indicated that overexpression of lamin B1 delays cell senescence. During the process of nucleophagy, appropriate nucleophagy can drive RAS-induced cell senescence and DNA damage-induced cell senescence so as to restrain cell proliferation. Besides, appropriate nucleophagy can degrade excessive amount of DNA content in polyploid tumor cells. Hence, selective nucleophagy may effectively protect cells from tumorigenesis and maintain cell and tissue integrity. However, excessive nucleophagy can attack normal cells and lead to an unforeseen cytotoxicity. In this paper, some signal pathways of nucleophagy occurrence were explained and the role of nucleophagy in these human diseases was analyzed. Our review indicates that nucleophagy may be a potential target in human diseases.
摘要：
Retracted Review article: Nucleophagy in Human Disease: Beyond the Physiological Role. [Tohoku J. Exp. Med., 2018, 244 (1), 75-81. doi: 10.1620/tjem.244.75.] The above Review article was published online on January 27, 2018. Soon after its publication (on February 1, 2018), Dr. Nian Fu and Prof. Linxi Chen informed the Editor-in-Chief, The Tohoku Journal of Experimental Medicine (TJEM), about serious violation of publication ethics. Indeed, Dr. Nian Fu and Prof. Linxi Chen were astonished to find their names as coauthors of this Review article, because they were not involved in the submission process of this Review article and they do not know any of other coauthors. In addition, the Review article is similar to their unpublished manuscript. After a thorough investigation in accordance with the recommendations of the Committee on Publication Ethics (COPE), the Editor-in-Chief of TJEM decided to retract this Review article. The reasons for Retraction are summarized below: forged authors and an unexpected case of plagiarism. Forged authors: Dr. Nian Fu and Prof. Linxi Chen were added as co-authors of the Review article without their knowledge. In fact, the signature provided by Prof. Linxi Chen is apparently different from the signature of a coauthor, named Linxi Chen, on the AUTHORS' RESPONSIBILITY FORM, provided by the corresponding author of the Review article. More critically, the signature provided by Dr. Nian Fu is completely different from the signature of Nian Fu, because the Chinese characters are different between the two signatures. In addition, the replies from three authors (Ming Zhou, Hongwen Ji and Yong Xia) clearly indicate that they misunderstand the identity of Dr. Nina Fu. We also attempted to contact two authors, named Nian Fu and Linxi Chen, via e-mail. As expected, the forged authors did not respond to our inquiries, despite that their e-mail addresses appear to be active. An unexpected case of plagiarism: This Review article is similar to the unpublished manuscript prepared by Dr. Nian Fu and Prof. Linxi Chen. Moreover, two figures used in the Review article are identical to the preliminary figures of their unpublished manuscript. According to Dr. Nian Fu, a local agency for language editing had transferred their unpublished manuscript to a third party. Unfortunately, the check system of TJEM is not effective for plagiarism of unpublished materials. We believe that the corresponding author of the Review article included the names of the original two authors to avoid the criticism of plagiarism. Eventually, the corresponding author agreed to retract the Review article.We apologize for any inconvenience caused by this retraction to readers. We also hope that the publication of the plagiarized Review article will not trouble Dr. Nian Fu and Prof. Linxi Chen too much.
作者：
Kai Zhang;Qionglin Zhou;Yu Guo;Linxi Chen;Lanfang Li
期刊：
生物化学与生物物理学报,2018年50(6):618-619 ISSN：1672-9145
通讯作者：
Linxi Chen<&wdkj&>Lanfang Li
作者机构：
[Zhang Kai; Zhou Qionglin; Guo Yu; Chen Linxi; Li Lanfang] Institute of Pharmacy and Pharmacology, University of South China, Learning Key Laboratory for Pharmacoproteomics;[Zhang Kai; Zhou Qionglin; Guo Yu; Chen Linxi; Li Lanfang] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001
通讯机构：
[Linxi Chen; Lanfang Li] L
关键词：
线粒体;机能障碍;蜂窝;胃;真核细胞;膜;细胞器;房间
摘要：
Both endoplasmic reticulum (ER) and mitochondria are fundamental organelles that coordinate high-order cell functions. ER is an extensive network of cisternae and microtubules, which stretches from the nuclear envelope to the cell surface in all eukaryotic cells. ER works as the site for protein synthesis and corrects post-translational ‘folding’ of proteins. ER also has the ability to transport proteins to their destination. Moreover, ER acts as a calcium ion (Ca~(2+)) reservoir which can be activated by both electrical and chemical stimulation.
作者机构：
[Fu, Nian; Chen, Linxi; Zhao, Hong] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China, Hengyang, 421001, China;[Yao, Pingbo] Intensive Care Units of the Affiliated Nanhua Hospital, University of South China, Hengyang, 421002, China
通讯机构：
[Nian Fu; Linxi Chen] I;Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China, Hengyang, China
关键词：
hypoxia;liver
摘要：
Hepatocellular carcinoma (HCC),one of the most common malignant cancers, is the third leading cause of cancer-related mortality worldwide. The etiological factors of HCC include alcohol intake, smoking, viral infections, cirrhosis, non-alcoholic steatohepatitis, hemochromatosis, and diabetes. Nowadays, despite much advance in HCC treatment, the 5-year survival rate for patients keeps dismal due to recurrence and metastases of HCC. Cancer stem cells (CSCs), also termed tumor-initiating cells, have the capability for unrestricted cell division, contributing to heterogeneous cell progenies. CSCs exist in both solid tumors and hematological malignancy. Till now, some cell surface markers are widely used to identify a subpopulation of cells with CSC features in liver such as CD24,CD 133, and epithelial cell adhesion molecule. Therefore, identification of CSC subpopulations in tumor will provide a novel understanding for cancer progress.
摘要：
Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in various diseases through different signal pathways. In this review, we discuss the possible mechanisms by which the Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase (PI3K)/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion (l/R) injury, pulmonary artery hypertension, retinal neovascular disease, acute renal injury, skeletal homeostasis, and gastrointestinal diseases. Apelin/APJ system decreases myocardial infarction size and alleviates myocardial l/R injury by inhibiting cardiomyocytes apoptosis. However, Apelin/APJ system improves pulmonary artery hypertension via increasing apoptosis. Apelin/APJ system exerts neuroprotective effect by blocking apoptosis and participates in the recovery of retinal neovascular disease by suppressing apoptosis. Apelin/APJ system also shows anti-apoptotic effect against acute renal injury and plays a role in regulating skeletal homeostasis. In gastrointestinal disease, Apelin/APJ system plays a potential physiological role in gastrointestinal cytoprotection by regulating apoptosis. We hope that a better understanding of the Apelin/APJ system will help to discover new disease pathogenesis and find possible therapeutic targets of the Apelin/APJ system essential for various diseases.
摘要：
Sirtuin 6 (SIRT6) is an important modulator of cardiovascular functions in health and diseases. However, the exact role of SIRT6 in heart disease is poorly defined. We hypothesized that SIRT6 is a negative regulator of angiotensin II (Ang II)-mediated myocardial remodeling, fibrosis and injury. The male Sprague-Dawley rats were randomized to Ang II (200 ng/kg/min) infusion with an osmotic minipump and pretreated with recombinant plasmids adeno-associated viral vector (AAV)-SIRT6 (pAAV-SIRT6) or pAAV-GFP for 4 weeks. Ang II triggered downregulated levels of SIRT6 and angiotensin-converting enzyme 2 (ACE2) and upregulated expression of connective tissue growth factor (CTGF) and proinflammatory chemokine fractalkine (FKN), contributing to enhanced cardiac fibrosis and ultrastructural injury. Reduced levels of phosphorylated pAMPK-alpha, increased myocardial hypertrophy and impaired heart dysfunction were observed in both Ang II-induced hypertensive rats and ACE2 knockout rats, characterized with increases in heart weight and left ventricular (LV) posterior wall thickness and decreases in LV ejection fraction and LV fractional shortening. More importantly, pAAV-SIRT6 treatment strikingly potentiated cardiac levels of pAMPKalpha and ACE2 as well as decreased levels of CTGF, FKN, TGFbeta1, collagen I and collagen III, resulting in alleviation of Ang II-induced pathological hypertrophy, myocardial fibrosis, cardiac dysfunction and ultrastructural injury in hypertensive rats. In conclusion, our findings confirmed cardioprotective effects of SIRT6 on pathological remodeling, fibrosis and myocardial injury through activation of AMPK-ACE2 signaling and suppression of CTGF-FKN pathway, indicating that SIRT6 functions as a partial agonist of ACE2 and targeting SIRT6 has potential therapeutic importance for cardiac fibrosis and heart disease.
作者机构：
[Liqun Lu; Jiangang Cao; Lanfang Li; Linxi Chen] 1 Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Learning Key Laboratory for Pharmacoproteomics , University of South China , Hengyang 421001 , China
通讯机构：
[Lanfang Li; Linxi Chen] 1;1 Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Learning Key Laboratory for Pharmacoproteomics , University of South China , Hengyang 421001 , China
关键词：
adult;embryo;ligands
摘要：
Apelin is an endogenous ligand of the APJ receptor (also known as Aplnr) which is a G protein-coupled receptor. Elabela (also known as Toddler, Apela), which shares little sequence similarity with Apelin (Fig.1),has been identified as a new endogenous ligand for APJ receptor. Elabela is encoded by AK092578 gene from a region of the human genome which was previously classified as 'non-coding'. Elabela is initially translated into a peptide of 54 amino acids including a secretory signal peptide. However, its mature form only contains 32 amino acids. The Elabela/Aplnr axis mainly acts in embryonic development compared with Apelin/APJ system which has abundant biological functions in different physiological and pathological processes. During zebrafish embryogenesis, Elabela is proved to be indispensable for the proper differentiation of endodermal precursors which guide the overlying cardiac progenitors to the heart-forming region to initiate cardiogenesis. Therefore, loss of Elabela causes severe cardiac dysplasia ranging from a rudimentary heart to no heart, and has little to no blood circulation. Elabela expresses concomitantly with Aplnr before the onset of gastrulation, and loss of Elabela phenocopies the loss of Aplnr during early heart development. However, Apelin is not expressed until midgastrulation and Apelin zebrafish morphants are not presented with overt congenital cardiac anomalies. Thus, the Elabela/Aplnr axis appears to be exclusive for endoderm differentiation and subsequent cardiogenesis (Fig.2).
摘要：
Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001–2 μmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4). Knockdown of Nox4 with siRNAs effectively prevented the reduction of GSH/GSSG ratio in apelin-13-treated cells. Furthermore, apelin-13 treatment dose-dependently increased the expression of Bip and CHOP, two ER stress markers, in the cells. Knockdown of APJ or Nox4 with the corresponding siRNAs, or application of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP expression. Moreover, apelin-13 treatment increased the formation of autophagosome and ER fragments and the LC3 puncta in the ER of the cells. Knockdown of APJ, Nox4, Bip or CHOP with the corresponding siRNAs, or application of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-II/I and beclin 1. Finally, knockdown of Nox4, Bip or CHOP with the corresponding siRNAs, or application of salubrinal significantly suppressed apelin-13-induced increases in the cell diameter, volume and protein contents. Our results demonstrate that ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.
作者机构：
[Li Lanfang; Zhou Qionglin; Li Xiaoxiao; Chen Linxi] Institute of Pharmacy and Pharmacology, University of South China, Learning Key Laboratory for Pharmacoproteomics;[Li Lanfang; Zhou Qionglin; Li Xiaoxiao; Chen Linxi] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001
通讯机构：
[Linxi Chen] 1
摘要：
The apelin receptor gene, also known as APJ or angiotensin receptor-like 1, was first cloned in 1993. APJ has strong sequence homology with the angiotensin II receptor (AT1); 54% for intrans membrane domains and 31% for the entire sequence. Nevertheless, APJ does not bind with angiotensin II. In 1998, Apelin, the first endogenous ligand for APJ, was identified in bovine stomach extracts. Both apelin and APJ are widely expressed in various tissues including the heart, brain, limbs, retina, liver, lung, skin, kidney, adipose tissue, and so on [1].
作者机构：
[Lu He] Department of Neurosurgery, First Affiliated Hospital, University of South China, Hengyang, 421001, China;[Linxi Chen] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug StudyUniversity of South China, Hengyang, 421001, China;[Lanfang Li] Department of Neurosurgery, First Affiliated Hospital, University of South China, Hengyang, 421001, China. llanfang6@126.com;[Lanfang Li] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug StudyUniversity of South China, Hengyang, 421001, China. llanfang6@126.com
通讯机构：
[Li, Lanfang] D;Department of Neurosurgery, First Affiliated Hospital, University of South China, Hengyang, 421001, China.;Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug StudyUniversity of South China, Hengyang, 421001, China.
关键词：
Crosstalk;Immune;Diseases
摘要：
Recently, Richter et al. [1] revealed the potential functions of the interaction between the serine/threonine kinase Tank-binding kinase 1 (TBK1) and the autophagy receptor optineurin (OPTN). The TBK1-OPTN axis targets damaged mitochondria for degradation via PINK1/parkin-mediated mitophagy [2, 3]. Indeed, TBK1 can phosphorylate OPTN at Ser177, Ser473, or Ser513 to enhance the binding capacity of OPTN with poly-ubiquitin (poly-UB) chains. Conversely, binding of poly-UB chains to OPTN is essential for the efficient recruitment and activation of TBK1 on mitochondria. These processes (Fig. 1) point toward an essential role of TBK1-OPTN signaling in mitochondrial quality control and maintaining cellular homeostasis. Currently, some studies have just focused on the role of the autophagy receptors OPTN, NDP52 (nuclear dot protein 52 kDa; also known as CALCOCO2, calciumbinding and coiled-coil domain 2), TAX1BP1 (Tax1 binding protein 1), and p62/sequestosome (SQSTM1) in damaged mitochondria [4–6]. However, only OPTN promotes auto-phagosome formation around mitochondria via the microtubule-associated protein light chain 3 (MAP1LC3/LC3)-interacting region (LIR) domain and is sufficient to trigger mitophagy.
通讯机构：
[Li, Lanfang] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
摘要：
The G protein-coupled receptor APJ elicits cellular response to diverse extracellular stimulus. Accumulating evidence reveals that APJ receptor plays a prominent role in the cardiomyocyte adapting to hypertrophic stimulation. At present, it remains obscure that the regulatory mechanism of APJ receptor in myocardial hypertrophy. The natural endogenous ligands apelin and Elabela as well as agonists maintain high affinity for the APJ receptor and drive its internalization. Ligand-activated receptor internalization is mainly performed by clathrin-mediated endocytic pathway. Simultaneously, clathrin-mediated endocytosis takes participate in the occurrence and development of cardiac hypertrophy. In this study, we hypothesize that natural ligands and agonists induce the mechanosensitive APJ internalization via clathrin-mediated endocytosis. APJ internalization may contribute to the development of cardiac hypertrophy. The mechanosensitive APJ internalization via clathrin-mediated endocytosis may be a new molecular mechanism of cardiac hypertrophy. (C) 2016 Elsevier Ltd. All rights reserved.
