摘要：
Truttmann MC et al.[1] recently reported that AMPylation of heat shock protein 70 (HSP70) family of chaperones participates in altering the aggregation properties and maintaining protein homeostasis (proteostasis), thereby playing a vital role in the development of neurodegenerative diseases (NDs). NDs are commonly manifested by protein aggregates, which exert harmful effects on proteostasis. Interestingly, it has been observed that AMPylation of heat shock proteins (HSPs) can maintain proteostasis by inhibiting the formation of protein aggregates. As previous studies only indicate that HSPs could regulate proteostasis, such a novel discovery further demonstrates the involvement of HSP70 AMPylation in the regulation of protein aggregation and the maintenance of proteostasis. Therefore, AMPylation can be considered to possess a therapeutic potential to target certain physiological processes related to proteostasis, such as age-related diseases.
摘要：
Apelin is the endogenous ligand for the G protein-coupled receptor APJ. Both apelin and APJ receptor are distributed in vascular smooth muscle cells (VSMCs) and play important roles in the cardiovascular system. Our previous reports have indicated that apelin-13 promoted the proliferation of VSMCs, but its exact mechanism remains to be further explored. The results of the present study demonstrated that the Warburg effect plays a pivotal role in apelin-13-induced human aortic vascular smooth muscle cells (HA-VSMCs) proliferation. Apelin-13 promoted the expression of glucose transporter type 1 (GLUT1), pyruvate kinase 2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter 1 (MCT1), and monocarboxylate transporter 4 (MCT4) in a dose- and time-dependent manner. Moreover, apelin-13 increased the extracellular, intracellular lactate level, and decreased adenosine triphosphate level in HA-VSMCs. Furthermore, siRNA-PKM2 reversed extracellular and intracellular lactate generation and inhibited the proliferation of HA-VSMCs induced by apelin-13. Downregulation of LDHA also significantly prevented extracellular and intracellular lactate generation and inhibited the proliferation of HA-VSMCs induced by apelin-13. Taken together, our results demonstrated a novel mechanism for HA-VSMCs proliferation induced by apelin-13 via Warburg effect.
作者机构：
[Yao P.; Cao J.] Affiliated Nanhua Hospital of University of South China, Hengyang, 421002, China;[Zhao H.; Chen L.] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study, University of South China, Hengyang, 421001, China
通讯机构：
[Jiangang Cao] A;[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<&wdkj&>Affiliated Nanhua Hospital of University of South China, Hengyang, China
摘要：
Pancreatitis, the pancreas digestion itself as well as its surroundings, is a potentially fatal disease involved in severe public health care burdens [1]. It is broadly classified into acute and chronic pancreatitis. The incidence of acute pancreatitis is 13–45 cases per 100,000 persons each year worldwide. Compared with acute pancreatitis, chronic pancreatitis, although lower in prevalence than acute pancreatitis, has profound effects on the patient’s quality of life. It has long been recognized that the pancreas is prominently sensitive to mechanical injury, which in turn triggers the occurrence of pancreatitis. For instance, gallstones are the most common cause for acute pancreatitis and the increased pressure within the gland could be responsible for gallstone pancreatitis [2]. In addition, endoscopic retrograde cholangiopancreatography (ERCP) carries a risk of post- ERCP pancreatitis. And it is believed that the acute pancreatitis induced by ERCP is due to the increased intraductal pressure [3]. Furthermore, in the process of surgery, manipulation of the pancreas can trigger acute pancreatitis, which is complicating postoperative recovery [4]. Therefore, it is widely believed that the pancreas itself is sensitive to mechanical forces.
关键词：
Apelin-13;Cardiomyocytes hypertrophy;Ferritin;Ferritinophagy;Mitochondria iron overload;ROS;sideroflexin1
摘要：
Excess iron accumulation and cardiac oxidative stress have been shown as important mediators of cardiac hypertrophy, whereas it remains largely elusive about the occurrence of mitochondrial iron overload and its significance during cardiac hypertrophy. In the present study, we aim to investigate the role of NCOA4-mediated ferritinophagy and SFXN1-dependent mitochondria iron overload in apelin-13-induced cardiomyocytes hypertrophy. Apelin-13 significantly promotes ferric citrate (FAC)-induced total cellular and mitochondria ion production, as well as mitochondria ROS contents. Mechanistically, apelin-13 effectively induces the expression of SFXN1, a mitochondria iron transporting protein and NCOA4, a cargo receptor of ferritinophagy in dose and time-dependent manner. Conversely, blockade of APJ by F13A abolishes these stimulatory effects. In addition, apelin-13-triggered mitochondria iron overload is reversed by the genetic inhibition of SFXN1 and NCOA4. NCOA4 deficiency via its silencing also interferes with the enhanced expression of SFXN1 evoked by apelin-13. In apelin-13-treated H9c2 cells, the promotion in cell diameter, volume as well as protein contents are obviously suppressed by the knockdown of NCOA4 and SFXN1 with their corresponding siRNAs. Remarkably, the human and murine hypertrophic hearts models, as well as apelin-13-injected mice models, present evident cardiac mitochondrial iron deposition and raised expressions of NCOA4 and SFXN1. Taken together, these results provide experimental evidences that NCOA4-mediated ferritinophagy might be defined as an essential mechanism leading to apelin-13-cardiomyocytes hypertrophy in SFXN1-dependent mitochondria iron overload manners.
通讯机构：
[Huang, Z; Chen, LX] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Inst Pharm & Pharmacol, Hengyang, Peoples R China.
关键词：
autophagy;megakaryocytes;mitophagy;platelets
摘要：
Platelets, developed from megakaryocytes, are characterized by anucleate and short-life span hemocyte in mammal vessel. Platelets are very important in the cardiovascular system. Studies indicate the occurrence of autophagy platelets and megakaryocytes. Moreover, abnormal autophagy decreases the number of platelets and suppresses platelet aggregation. In addition, mitophagy, as a kind of selective autophagy, could inhibit platelet aggregation under oxidative stress or hypoxic, whereas promote platelet aggregation after reperfusion. Finally, autophagy regulates hemorrhagic and thrombosis diseases by influencing the number and function of platelets. In this paper, the role of autophagy in platelets and megakaryocytes, as well as coupled with the promotive or inhibitory role of hemorrhagic and thrombosis diseases are elucidated. Therefore, autophagy may be a potentially therapeutic target in modulating the platelet-related diseases.
作者机构：
[Hong Zhou; Lu He; Lin-Xi Chen] Department of Radiology,First Affiliated Hospital,University of South China;[Hong Zhou; Lu He; Lin-Xi Chen] Institute of Pharmacy and Pharmacology,Hunan Province Cooperative Innovation Center for Molecular Target New Drugs Study,University of South China
会议名称：
2018 International Neural Regeneration Symposium(INRS2018), 11th Asia Pacific Symposium on Neural Regeneration (APSNR2018)and 2018 International Spinal Cord Injury Treatments & Trials Symposium (ISCITT2018)
会议时间：
2018-07-26
会议地点：
中国广东广州
摘要：
APJ, an orphan G protein-coupled receptor, is first identified through homology cloning in 1993. Apelin/APJ system is widely expressed in many kinds of cells, especially in vascular smooth muscle cell
期刊：
JOURNAL OF CELLULAR PHYSIOLOGY,2018年233(3):2075-2090 ISSN：0021-9541
通讯作者：
Li, Lanfang
作者机构：
[Li, Lanfang; Xu, Jin; Chen, Linxi] Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Hengyang, Peoples R China.;[Li, Lanfang] Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
通讯机构：
[Li, Lanfang] U;Univ South China, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
关键词：
ATP;oxidative stress;pannexins
摘要：
Pannexins, which contain three subtypes: pannexin-1, -2, and -3, are vertebrate glycoproteins that form non-junctional plasma membrane intracellular hemichannels via oligomerization. Oxidative stress refers to an imbalance of the generation and elimination of reactive oxygen species (ROS). Studies have shown that elevated ROS levels are pivotal in the development of a variety of diseases. Recent studies indicate that the occurrence of these oxidative stress related diseases is associated with pannexin hemichannels. It is also reported that pannexins regulate the production of ROS which in turn may increase the opening of pannexin hemichannels. In this paper, we review recent researches about the important role of pannexin hemichannels in oxidative stress related diseases. Thus, pannexin hemichannels, novel therapeutic targets, hold promise in managing oxidative stress related diseases such as the tumor, inflammatory bowel diseases (IBD), pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), cardiovascular disease, insulin resistance (IR), and neural degeneration diseases.
作者机构：
[Tang Mingzhu; Lu Liqun; Huang Zhen; Chen Linxi] Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China,Learning Key Laboratory for Pharmacoproteomics, Hengyang, 421001
通讯机构：
[Zhen Huang; Linxi Chen] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
关键词：
signal transduction;mitochondria
摘要：
Acta Biotheoretica is devoted to the promotion of theoretical biology, encompassing mathematical biology and the philosophy of biology, paying special attention to the methodology of formation of biological theory. Papers on all kind of biological theories are welcome. Interesting subjects include philosophy of biology, biomathematics, computational biology, genetics, ecology and morphology. The process of theory formation can be presented in verbal or mathematical form. Moreover, purely methodological papers can be devoted to the historical origins of the philosophy underlying biological theories and concepts. Papers should contain clear statements of biological assumptions, and where applicable, a justification of their translation into mathematical form and a detailed discussion of the mathematical treatment. The connection to empirical data should be clarified. Acta Biotheoretica also welcomes critical book reviews, short comments on previous papers and short notes directing attention to interesting new theoretical ideas. Coverage in the Journals&commat;Ovid database begins with the first 1997 issue.
摘要：
APJ, an orphan G protein-coupled receptor, is first identified through homology cloning in 1993. Apelin is endogenous ligand of APJ extracted from bovine stomach tissue in 1998. Apelin/APJ system is widely expressed in many kinds of cells such as endothelial cells, cardiomyocytes, especially vascular smooth muscle cell. Vascular smooth muscle cell (VSMC), an integral part of the vascular wall, takes part in many normal physiological processes. Our experiment firstly finds that apelin/APJ system enhances VSMC proliferation by ERK1/2-cyclin D1 signal pathway. Accumulating studies also show that apelin/APJ system plays a pivotal role in mediating the function of VSMC. In this paper, we review the exact role of apelin/APJ system in VSMC, including induction of proliferation and migration, enhance of contraction and relaxation, inhibition of calcification. Furthermore, we discuss the role of apelin/APJ system in vascular diseases, such as atherosclerosis, hypertension, and chronic kidney disease (CKD) from the point of VSMC. Above all, apelin/APJ system is a promising target for managing vascular disease.
摘要：
Olfactory receptors (ORs) are mainly distributed in olfactory neurons and play a key role in detecting volatile odorants, eventually resulting in the production of smell perception. Recently, it is also reported that ORs are expressed in non-olfactory tissues including heart, lung, sperm, skin, and cancerous tissues. Interestingly, ectopic ORs are associated with the development of diseases in non-olfactory tissues. For instance, ectopic ORs initiate the hypoxic ventilatory responses and maintain the oxygen homeostasis of breathing in the carotid body when oxygen levels decline. Ectopic ORs induce glucose homeostasis in diabetes. Ectopic ORs regulate systemic blood pressure by increasing renin secretion and vasodilation. Ectopic ORs participate in the process of tumor cell proliferation, apoptosis, metastasis, and invasiveness. Ectopic ORs accelerate the occurrence of obesity, angiogenesis and wound-healing processes. Ectopic ORs affect fetal hemoglobin levels in sickle cell anemia and thalassemia. Finally, we also elaborate some ligands targeting for ORs. Obviously, the diversified function and related signal pathway of ectopic ORs may play a potential therapeutic target in non-olfactory tissues. Thus, this review focuses on the latest research results about the diversified function and therapeutic potential of ectopic ORs in non-olfactory tissues.
作者机构：
[Liqun Lu; Mingzhu Tang] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China;[Feng Xie] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China. 764136587@qq.com;[Linxi Chen] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China. lxchen6@126.com
通讯机构：
[Feng Xie; Linxi Chen] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China<&wdkj&>Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomics, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
关键词：
Critical Mechanism;Neuronal Function;Fragile X Mental Retardation Protein (FMRP);Small Ubiquitin-like Modifier (SUMO);methyl-CpG-binding Protein 2 (MeCP2)
摘要：
Recently,Khayachi et al.showed that fragile X mental retardation protein (FMRP) is an active substrate of the small ubiquitin-like modifier (SUMO) pathway in neurons.FMRP SUMOylation is induced by the activation of metabotropic glutamate receptors (mGlu5Rs).FMRP SUMOylation is required for dissociating FMRP from dendritic RNA granules and controlling spine density and proper maturation.Mechanically,the SUMOylation process is triggered by the activation of mGlu5Rs,thereby contributing to maintaining FMRP-mediated neuronal function.In fact,some proteins that mediate synaptic plasticity,neurotransmitter release,and neuronal network formation,are mostly regulated by SUMOylation.Therefore,SUMOylation has emerged as an essential posttranslational modification in the nervous system.This novel discovery first provides evidence to support the idea that FMRP is a novel substrate of SUMOylation and acts as an essential regulator in the developing brain.Clearly,it also expands the biological ramifications of FMRP modification,since FMRP was previously supposed to be modulated by phosphorylation and dephosphorylation.Together,their research reveals that the rapid SUMOylation of FMRP results from the activation of mGlu5Rs and activity-dependent FMRP SUMOylation is a novel target for affecting neuronal functions.
期刊：
JOURNAL OF CELLULAR PHYSIOLOGY,2018年233(9):6472-6482 ISSN：0021-9541
通讯作者：
Li, Lanfang;Jiang, Zhisheng
作者机构：
[Li, Lanfang; Xu, Jin; Chen, Linxi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;[Jiang, Zhisheng] Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang, Hunan, Peoples R China.
通讯机构：
[Li, Lanfang; Jiang, Zhisheng] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Inst Pharm & Pharmacol, Hengyang 421001, Hunan, Peoples R China.;Univ South China, Inst Cardiovasc Dis, Key Lab Arteriosclerol Hunan Prov, Hengyang, Hunan, Peoples R China.
关键词：
apelin;APJ;elabela
摘要：
The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely expressed throughout human body. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, fluid homeostasis, and energy metabolism regulation. Recently, a new endogenous peptidic ligand of APJ, named Elabela, has been identified and shown to play a crucial role in embryonic development. In addition, increasing evidences show that Elabela is also intimate associated with a large number of physiological processes in adulthood. However, a comprehensive summary of Elabela has not been reported to date. In this review, we provide an overview of the biological functions of Elabela. Collectively, Elabela, a potential therapeutic peptide, exerts diverse biological functions in both embryos and adult organisms, such as dysontogenesis, self-renewing of human embryonic stem cells, endoderm differentiation, heart morphogenesis, cardiac dyfunctions, blood pressure control, angiogenesis, blood pressure control, regulation of food and water intake, bone formation, and kidney diseases.
