通讯机构：
[Chen, Linxi; Li, Lanfang] I;Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, China. Electronic address:
作者机构：
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;[Fu N.] Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang Hunan, China;[Li L.; Zhang K.] 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;[Wang L.] 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, Department of Gastroenterology, Affiliated Nanhua Hospital, University of South China, Hengyang Hunan, China
通讯机构：
[Li, L.] I;Institute of Pharmacy and Pharmacology, China
关键词：
MCU;BLOCKS;critical
摘要：
Mitochondrial calcium uniporter (MCU) is a highly selective Ca~(2+) channel protein of the mitochondria inner membrane [1], which allows divalent cations (Ca~(2+) ≈Sr~(2+) >>Mn~(2+) ≈Ba~(2+)) to permeate [2]. The MCU is a 40-kDa protein that contains a proteolytically cleaved mitochondrial import sequence, two coiled-coil domains, two transmembrane domains, and a short motif of amino acids between the two transmembrane domains critical for Ca~(2+) transport [3]. MCU is widely expressed in the mitochondrial inner membrane of various cells [4]. In addition, MCU is also a highly conserved protein among different species (Fig. 1A), suggesting that MCU may play an essential role in the process of physiology and pathology.
作者机构：
[Li, Lanfang; Zhang, Kai; Chen, Linxi] Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Pharm & Pharmacol, Learning Key Lab Pharmacoprote, Hengyang 421001, Peoples R China.;[Cao, Jiangang] Univ South China, Affiliated Nanhua Hosp, Clin Res Inst, Hengyang 421002, Peoples R China.;[He, Lu] Univ South China, Affiliated Hosp 1, Dept Neurosurg, Hengyang 421001, Peoples R China.;[Zhang, Zidong] St Louis Univ, Coll Publ Hlth & Social Justice, St Louis, MO 63103 USA.
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.
关键词：
Cancer;Cardioprotection;FAT10;FAT10ylation;Protein degradation;Ubiquitin-like protein
摘要：
As a member of the ubiquitin-like protein family, the human leukocyte antigen F locus adjacent transcript 10 is composed of two ubiquitin-like domains that have high homology with ubiquitin. Studies have shown that abnormal FAT10 expression and FAT10ylation are crucial to many aspects of cellular biology, such as protein degradation, immune response, regulation of apoptosis and cell cycle progression. In this manuscript, we review some important biological roles of FAT10 in cardioprotection and tumor promotion. FAT10 may be cardioprotective in ischemia and hypoxia through attenuation of hypoxia-induced cardiomyocyte apoptosis regulated by the BCL2/BAX ratio and caveolin-3. In addition, FAT10 may be a novel cancer biomarker that contributes to proliferation, invasion, and metastasis in a broad spectrum of cancer cells, including hepatocellular carcinoma (HCC), glioma, and gastric carcinoma. These findings imply that FAT10 will be a candidate target during treatment of cardiovascular conditions due to its cardioprotective effect. Moreover, FAT10 is a potential therapeutic target in cancer.
通讯机构：
[Chen, LX; Li, LF] U;Univ South China, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Learning Key Lab Pharmacoprote, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
Berberine;Cardiovascular diseases;Endoplasmic reticulum stress;Ischemia reperfusion injury;Schisandrin B;Unfolded protein response
摘要：
Endoplasmic reticulum (ER) is an intracellular membranous organelle involved in the synthesis, folding, maturation and post-translation modification of secretory and transmembrane proteins. Therefore, ER is closely related to the maintenance of intracellular homeostasis and the good balance between health and diseases. Endoplasmic reticulum stress (ERS) occurs when unfolded/misfolded proteins accumulate after disturbance of ER environment. In response to ERS, cells trigger an adaptive response called the Unfolded protein response (UPR), which helps cells cope with the stress. In recent years, a large number of studies show that ERS can aggravate cardiovascular diseases. ERS-related proteins expression in cardiovascular diseases is on the rise. Therefore, down-regulation of ERS is critical for alleviating symptoms of cardiovascular diseases, which may be used in the near future to treat cardiovascular diseases. This article reviews the relationship between ERS and cardiovascular diseases and drugs that inhibit ERS. Furthermore, we detail the role of ERS inhibitors in the treatment of cardiovascular disease. Drugs that inhibit ERS are considered as promising strategies for the treatment of cardiovascular diseases.
作者机构：
[Yiyuan Yang; Lanfang Li; Kai Zhang; 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, China
通讯机构：
[Li, L.] I;Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, China
摘要：
Cardiomyocytes, also known as myocardial fibers, are the muscle cells which form the heart tissue. Previous studies have indicated that fetal mammalian cardiomyocytes maintain the regeneration capacity, which promotes the fetal heart growth. Regardless of environment insults including nutrient deprivation, changes of blood flow, along with mechanical and volume loading [1], embryonic mammalian cardiac muscle cells are also related to robust proliferation response. Similarly, the hearts of 1-day-old neonatal mice could also be fully regenerated after surgical resection of the left ventricular apex or myocardial infarction (MI) [2]. Intriguingly, studies have also shown that certain fish, such as adult zebrafish, or urodele amphibians retain an observable capacity for regeneration [3]. In response to cardiac damage, zebrafish exhibits complete regeneration primarily due to the proliferation of cardiomyocytes. Nevertheless, the mouse heart loses this potential in the first week after birth. Tragically, it has been demonstrated that the adult mammalian cardiomyocyte unable to proliferate (Fig. 1A). Adult heart is considered as a terminally differentiated organ [4] that has limited capacity for cardiomyogenesis. Therefore, patients suffering from cardiovascular failure are unable to repair the heart and survive after MI or other heart diseases. Therefore, finding a feasible approach to stimulate adult mammalian cardiomyocyte proliferation is beneficial for the treatment of MI and other heart 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.
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.
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.
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.
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.
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：
Chen, L.
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：
[Chen, L.] I
关键词：
apoptosis;APELIN
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.
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.
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：
Chen, L.
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：
[Chen, L.] 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.
