Univ South China, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.
Apelin/APJ system;Cardiac hypertrophy;Oxidative stress;Obesity;Hypertension;Myocardial infarction;AT1R;angiotensin II type 1 receptor;Ang II;angiotensin II;PCSK3;proprotein convertase subtilisin/kexin3;5-HT;serotonin;TNF-α;tumor necrosis factor-a;HW/BW;the ratio of heart weight/body weight;ANP;atrial natriuretic peptide;LV;left ventricular;ANF;atrial natriuretic factor;TGF-β1;transforming growth factor beta1;ROS;reactive oxygen species;β-MHC;beta-myosin heavy chain;HFD;high-fat diet;ER;endoplasmic reticulum;FA;fatty acid;MI;myocardial infarction;ACE2;angiotensin-converting enzyme 2;LVH;left ventricular hypertrophy
Apelin acts as the endogenous ligand of G protein coupled receptors APJ. The apelin/APJ systemis responsible for the occurrence and development of cardiovascular diseases. In recent years, apelin/APJ has been considered to play an important role in cardiac hypertrophy, but whether that role is beneficial or aggravating remains controversial. Apelin/APJ alleviates cardiac hypertrophy which is triggered by angiotensin II, oxidative stress and exercise. However, central administration of apelin induces cardiac hypertrophy. Peripheral administration of apelin also promotes the development of cardiac hypertrophy under non-pathological conditions. Furthermore, our laboratory discovers that apelin/APJ is able to induce hypertrophy of cardiomyocytes in vitro. The exact mechanism of apelin/APJ's dual effects in cardiac hypertrophy requires further study. In this paper, we review the controversies associated with apelin/APJ in cardiac hypertrophy and we elaborate the role of apelin/APJ in cardiac hypertrophy related-diseases including obesity, diabetes, hypertension, myocarditis and myocardial infarction. We conclude that further studies should emphasize more about the relationship between apelin/APJ and pathological hypertrophy especially in clinical patients. Moreover, apelin/APJ can be a promising therapeutic target for cardiac hypertrophy. (C) 2016 Published by Elsevier Ireland Ltd.
Apelin is an endogenous ligand of seven‐transmembrane G protein‐coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, kidney, and even in tumor tissues. Studies show that apelin mRNA is highly expressed in the inner stripe of kidney outer medulla, which plays an important role in process of water and sodium balance. Additionally, more studies also indicate that apelin/APJ system exerts a broad range of activities in kidney. Therefore, we review the role of apelin/APJ system in kidney diseases such as renal fibrosis, renal ischemia/reperfusion injury, diabetic nephropathy, polycystic kidney disease, and hemodialysis (HD). Apelin/APJ system can improve renal interstitial fibrosis by reducing the deposition of extracellular matrix. Apelin/APJ system significantly reduces renal ischemia/reperfusion injury by inhibiting renal cell death. Apelin/APJ system involves the progression of diabetic nephropathy (DN). Apelin/APJ system also predicts the process of polycystic kidney disease. Besides, apelin/APJ system prevents some dialysis complications in HD patients. And apelin/APJ system alleviates chronic kidney disease (CKD) by inhibiting vascular calcification (VC). Overall, apelin/APJ system plays diversified roles in kidney disease and may be a potential target for the treatment of kidney disease.
Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non‐tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid β‐mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non‐tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non‐tumor diseases.
The Golgi apparatus (GA) is a ribbon‐like system of stacks which consist of multiple closely apposed flattened cisternae and vesicles usually localized in the juxta‐nuclear area. As for the biological functions, the GA plays a major role in protein biosynthesis, post‐translational modification, and sorting protein from ER to plasma membrane and other destinations. Structural changes and functional disorder of the GA is associated with various diseases. Moreover, increasing evidence revealed that swelling, poor development, and other morphological alterations of the GA are linked to cardiovascular diseases such as heart failure (HF), arrhythmia, and dilated cardiomyopathy. Furthermore, dysfunction of the GA is also related to cardiovascular diseases since the GA is extremely responsible for transport, glycosylation, biosynthesis, and subcellular distribution of cardiovascular proteins. This review gives a brief overview of the intricate relationship between the GA and cardiovascular diseases. In addition, we provide a further prospective that the GA may provide diagnosis reference for cardiovascular diseases, and changes in the ultrastructure and morphology of the GA such as swelling, poor development, and fragmentation may serve as a reliable index for cardiovascular diseases.
Acta Biochimica et Biophysica Sinica,2016年48(5):487-489 ISSN：1672-9145
[Li, Lanfang; Wu, Di] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China;[Chen, Linxi] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421001, China firstname.lastname@example.org
Cancer metastasis is a process that cancer cells deviate from the primary site and spread to the other areas to form new colonies, which is the leading cause of death in cancer patients. During metastatic progression, circulating cancer cells lodge within the microvasculature of end organs, where most of them die from mechanical deformation. However, cancer cells can survive from mechanical deformation by unknown mechanisms. Recently, Furlow et al. identified a mutation truncated form of pannexin-1 (Panx-1), PANX1~(1–89), which was significantly enriched in highly metastatic cancer cells. PANX1~(1–89) augmented Panx-1 channel-mediated adenosine triphosphate (ATP) release and enhanced the efficiency of metastasis by promoting metastatic breast cancer cells survival during physical deformation. Additionally, carbenoxolone (CBX), a Panx-1 inhibitor, was proved to reduce the efficiency of breast cancer metastasis. These results suggested that Panx-1 is one of the molecular bases for metastatic cell survival in microvasculature-induced biomechanical trauma.
<正>Aim:Caveolae and caveolin-1participate in the transportation ofcholesterol and cell signal transduction.Our previous studies showed thatthe inhibitory effect of calcitonin gene-related peptide(CGRP