摘要：
Myristica fragrans is a traditional herbal medicine and has been shown to alleviate the development of atherosclerosis. However, the anti-atherogenic mechanisms of M. fragrans are still to be addressed. In this study, we explored the effect of M. fragrans on lipid metabolism and inflammation and its mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction and western blot analysis results showed that M. fragrans promotes cholesterol efflux from THP-1-derived macrophages and reduces intracellular total cholesterol, cholesterol ester, and free cholesterol contents in a dose- and a time-dependent manner. Further study found that liver X receptor alpha (LXRα) antagonist GGPP significantly blocked the upregulation of ABCA1 expression with M. fragrans treatment. In addition, chromatin immunoprecipitation assay confirmed that GATA binding protein 3 (GATA3) can bind to the LXRα promoter, and inhibition of GATA3 led to the downregulation of LXRα and ATP-binding cassette subfamily A member 1 expression. Furthermore, M. fragrans reduced lipid accumulation, followed by decreasing tumor necrosis factor-α, interleukin (IL)-6, and IL-1β and increasing IL-10 produced by THP-1-derived macrophages. Therefore, M. fragrans is identified as a valuable therapeutic medicine for atherosclerotic cardiovascular disease.
作者机构：
[徐晓芳] Institute of Pharmaceutical Pharmacology, University of South China, Hunan, Hengyang, 421000, China;Department of Clinical Pharmacology, The Second Affiliated Hospital, University of South China, Hunan, Hengyang, 421000, China;Department of Pharmacy, The Affiliated Nanhua Hospital, University of South China, Hunan, Hengyang, 421000, China;[周玉生] Department of Clinical Pharmacology, The Second Affiliated Hospital, University of South China, Hunan, Hengyang, 421000, China, Department of Pharmacy, The Affiliated Nanhua Hospital, University of South China, Hunan, Hengyang, 421000, China;[李荣] Institute of Pharmaceutical Pharmacology, University of South China, Hunan, Hengyang, 421000, China, Department of Clinical Pharmacology, The Second Affiliated Hospital, University of South China, Hunan, Hengyang, 421000, China
通讯机构：
[Zhou, Y.-S.] D;Department of Clinical Pharmacology, Hunan, China
作者：
Tingting Duan;Cifei Tang;Zhuan Wu;Zhaohui Cao;Xiaobo Hu
期刊：
生物化学与生物物理学报,2021年53(1):128-130 ISSN：1672-9145
通讯作者：
Cao, Z.;Hu, X.
作者机构：
[Zhaohui Cao; Tingting Duan; Xiaobo Hu; Zhuan Wu; Cifei Tang] The Key Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province Department of Education,Department of Biochemistry, Hengyang Medical School, University of South China, Hengyang 421001, China
通讯机构：
[Cao, Z.; Hu, X.] T;The Key Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province Department of Education, China
关键词：
ENDOGENOUS;HOMEOSTASIS;CYTOKINE
摘要：
Type 2 diabetes (T2D) is a chronic metabolic disease characterized by insulin resistance and hyperglycemia, which is ultimately linked to the loss of pancreatic β-cells and their function [1]. Understanding the pathological mechanisms of β-cell dysfunction in T2D may lead to development of new therapeutic approaches. Recently, compelling evidence suggests that members of the nuclear receptor 4A (NR4A) subgroup play a pivotal role in β-cell loss [2].
摘要：
OBJECTIVE: Type 1 diabetes (T1D) results from dysfunction of pancreatic islets beta cells. Recent studies supported that endoplasmic reticulum (ER) stress takes an important role in pancreatic beta cell excessive loss, resulting in T1D. Here, we aimed to review the relationship between ER stress and T1D. Additionally, we also reviewed the potential mechanisms underlying ER stress mediated T1D. DATA SOURCES: This review was based on the articles from PubMed databases up to July 2019, with the following keywords: "endoplasmic reticulum stress", "inflammation", "autoimmunity", and "type 1 diabetes". STUDY SELECTION: Original articles and critical reviews on the topics were selected and carefully analyzed. RESULTS: Studies have shown that severe ER stress is directly involved in the pancreatic beta cells destruction and pathogenesis of T1D. CONCLUSIONS: ER stress plays a key part in pancreatic beta cells and T1D, which will help in developing new effective therapeutics for T1D.
作者机构：
[Zhao, Xiang] Univ South China, Peoples Hosp Huaihua 1, Dept Gen Practice, Huaihua 418000, Hunan, Peoples R China.;[Deng, Ye; Qiu, Cheng-Feng; Shi, Zhi-Hua; Deng, Zi-Wei; Shu, Yuan-Lu; Tang, Bin] Univ South China, Peoples Hosp Huaihua 1, Dept Evidence Based Med & Clin Ctr, Huaihua 418000, Hunan, Peoples R China.;[Deng, Ye; Qiu, Cheng-Feng; Shi, Zhi-Hua; Deng, Zi-Wei] Univ South China, Peoples Hosp 1, Dept Pharmacol, Huaihua 418000, Hunan, Peoples R China.;[Tan, Li-Ming] Second Peoples Hosp Huaihua City, Dept Pharmacol, Huaihua 418000, Hunan, Peoples R China.;[Jiang, Shi-Long] Cent South Univ, Xiangya Hosp, Dept Clin Pharmacol, Changsha 410008, Hunan, Peoples R China.
通讯机构：
[Qiu, Cheng-Feng] U;Univ South China, Peoples Hosp Huaihua 1, Dept Evidence Based Med & Clin Ctr, Huaihua 418000, Hunan, Peoples R China.
摘要：
Asialoglycoprotein receptor 1 (ASGR1) is the major subunit of ASGR, it is predominantly expressed by liver parenchymal cells and relatively lower expression was found in peripheral blood monocytes. A genetic study recently revealed that ASGR1 haploinsufficiency resulted from loss-of-function (LOF) variants was strongly associated with the pronounced reductions in serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, suggesting that ASGR1 may play a key role in cholesterol metabolism. However, the function of ASGR1 remains largely unclear. This study was focused on the association of ASGR1 gene expression in monocytes and plasma cholesterol level.
摘要：
Interleukin-5 (IL-5) is manifested as its involvement in the process of atherosclerosis, but the mechanism is still unknown. In this study, we explored the effect of IL-5 on lipid metabolism and its underlying mechanisms in THP-1-derived macrophages. The quantitative polymerase chain reaction (qPCR) and western blot analysis results showed that IL-5 significantly up-regulated ATP-binding cassette transporter A1 (ABCA1) expression in a dose-dependent and time-dependent manner. [3H]-labeled cholesterol was used to assess the levels of cholesterol efflux, and the results showed that IL-5 increased ABCA1-mediated cholesterol efflux. A high-performance liquid chromatography assay indicated that cellular cholesterol content was decreased by IL-5 treatment in THP-1-derived macrophages. The selective inhibitor and small interfering RNA were used to block the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway. The results of the qPCR and western blot analysis showed that IL-5 activated JAK2/STAT3 pathway to up-regulate ABCA1 expression. Meanwhile, IL-5 reduced the expression level of miR-211. Furthermore, we found that JAK2 is a target gene of miR-211 and miR-211 mimic inhibited the expression of JAK2 and reduced the levels of p-STAT3 and ABCA1 as revealed by luciferase reporter assay, qPCR and western blot analysis. In summary, these findings indicated that IL-5 promotes ABCA1 expression and cholesterol efflux through the miR-211/JAK2/STAT3 signaling pathway in THP-1-derived macrophages.
作者机构：
[Li Zhu; Qionglin Zhou; 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;[Lu He] Department of Pharmacy, The First Affiliated Hospital, University of South China, Hengyang 421001, China
通讯机构：
[Lu He] D;[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 421001, China<&wdkj&>Department of Pharmacy, The First Affiliated Hospital, University of South China , Hengyang 421001, China
关键词：
signal transduction;glycolysis;oxidative phosphorylation
摘要：
Iron regulatory protein 2 (IRP2), first separated from mouse in 1993,is a cytoplasmic iron-regulated RNA-binding protein. IRP2 is a subtype of iron regulatory proteins (IRPs). IRP2 binds to ironresponsive element (IRE) RNA sequence to maintain iron homeostasis [1]. IRP2 can easily be hydrolyzed by protease because of its unique sequence of 73 amino acids. In general, IRP2 is widely expressed in many tissues, including fat, lung, brain, stomach, liver, heart, thyroid, adrenal, lymph node, kidney, intestine and so on [2].
作者机构：
[洪陈亮; 王珍; 秦旭平] Lab of Vascular Biology, Institute of Pharmacy and Pharmacology, University of South China, Hunan, Hengyang, 421001, China;Dept of Clinical Pharmacy, the First People's Hospital of Huaihua, Hunan, Huaihua, 418000, China;[袁李佳龙] Lab of Vascular Biology, Institute of Pharmacy and Pharmacology, University of South China, Hunan, Hengyang, 421001, China, Dept of Clinical Pharmacy, the First People's Hospital of Huaihua, Hunan, Huaihua, 418000, China
通讯机构：
[Qin, X.-P.] L;Lab of Vascular Biology, Hunan, China
作者机构：
[Zhao Hong; Chen Lin Xi] Univ South China, Hengyang Med Coll, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;[Zhao Hong; Qiu Ting Ting] Univ South China, Coll Nursing, Hengyang 421001, Hunan, Peoples R China.;[Liu Mei Qing] Second Peoples Hosp Yunnan Prov, Dept Pharm, Kunming 650000, Yunnan, Peoples R China.
通讯机构：
[Chen Lin Xi] U;[Liu Mei Qing] S;Univ South China, Hengyang Med Coll, Inst Pharm & Pharmacol, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Hengyang 421001, Hunan, Peoples R China.;Second Peoples Hosp Yunnan Prov, Dept Pharm, Kunming 650000, Yunnan, Peoples R China.
关键词：
STORE;producing;FEEDING
摘要：
Mammalian adipose tissues can be broadly divided into white adipose tissue(WAT), beige adipose tissue, and brown adipose tissue(BAT)[1]. The function of WAT is to store superfluous energy and is characterized by unilamellar lipid droplets. WAT, as a prominent endocrine organ, regulates feeding and satiety by producing hormones. Compared with WAT, beige adipose tissue has some smaller multilocular lipid droplets and is located in WAT depots. However, BAT contains an abundance of mitochondria, uncoupling protein-1(UCP1), and multilocular lipid droplets[2]. BAT is an important non-shivering thermogenesis organ, with the capacity to oxidize metabolic substrates, including fatty acids and glucose, to produce heat. The main mechanism of heat production depends on UCP1. It transports protons into mitochondria, leading to the collapse of the proton gradient for oxidative phosphorylation; subsequently, cells generate heat instead of ATP. The thermogenic activity of brown adipocytes enables them to safeguard other tissues and themselves from lipid overaccumulation. Many studies have confirmed that promoting brown adipose thermogenic activity or the browning of white fat contributes to curbing obesity, diabetes,and other metabolic diseases[3-7]. Brown adipocytes are derived from Myf5+ progenitors with a high expression of PRDM16, BMP7, and PPARγ. These transcription regulators drive progenitors to develop into mature brown adipocytes[8]. Meanwhile, a development process is required for brown adipogenesis to suppress adipogenic inhibitors,including Wnt, necdin, and preadipocyte factor-1(Pref-1). Numerous studies have confirmed that many signaling pathways promote brown adipocyte differentiation, including rhACE2, SIRT5, RGS2,STAT3, RepSox, and SENP2(Figure 1). Tu et al.[9] reported that RepSox promoted brown preadipocyte differentiation by inhibiting TGF-β signaling. Shuai et al.[10] demonstrated that SIRT5 enhanced the expression of brown adipogenic promoters, including PPARγ and PRDM16. Klepac et al.[11] identified a crucial role for RGS2, which antagonized the inhibitory effect of Gq/Rho/ROCK signaling, in the acceleration brown adipogenesis. Cantwell et al.[12] revealed the significance of STAT3 in the early induction of primary Myf5+ brown adipogenesis through its suppression of Wnt/β-catenin signaling. Kawabe et al.[13] proved that rhACE2 increased the levels of PRDMl6 and PGC1α to boost differentiation of BAT. Recently, Liang et al.[14] demonstrated that brown adipocyte differentiation was facilitated via the SENP2-mediated deSUMOylation for necdin.
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：
[Yangt Yiyuan; Wangt Li; Li Lanfang; Chen Linxi] Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomic, 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
通讯机构：
[Linxi Chen; Lanfang Li] I;Institute of Pharmacy and Pharmacology, Learning Key Laboratory for Pharmacoproteomic, 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
关键词：
nervous system disorders;mitochondria;membrane proteins
摘要：
Connexins and pannexins are two kinds of transmembrane proteins, which play important physiological roles. Connexins form hemichannels and channels, mainly contributing to the formation of gap junctions. Pannexins are newly discovered gap junction proteins and their structures consist of intracellular N-termini, intracellular C termini, an intracellular loop, two extracellular loops, and four transmembrane regions [1]. Because the extracellular domains of pannexins contain glycosylated asparagine residues, pannexins cannot form intercellular channels [2], but in the plasma membrane they can form large pores that can be permeated by ions and other molecules such as ATP [3].
