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
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：
[Tang, Dan; Ou, Weiwei; Wang, Deming; Chen, Quan; Wang, Jiazheng; Xiao, Ji] Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;[Mo, Zhongcheng] Univ South China, Dept Histol & Embryol, Hengyang 421001, Peoples R China.;[Tang, Chaoke] Univ South China, Inst Cardiovasc Res, Life Sci Res Ctr, Key Lab Atherosclerol Hunan Prov, Hengyang 421001, Peoples R China.;[Peng, Liangyu] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
通讯机构：
[Wang, Deming; Peng, Liangyu] U;Univ South China, Affiliated Hosp 2, Dept Anesthesiol, Hengyang 421001, Peoples R China.;Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Peoples R China.
关键词：
liver X receptor;cytokine;mRNA decay;tristetraprolin;mitogen-activated protein kinase
摘要：
Liver X receptors (LXRs) have anti-inflammatory properties. Whether LXRs play a role in post-transcriptional control of inflammatory cytokine expression is not clear. Here, we firstly identified that the synthetic LXR agonist T0901317 promoted IL-1β, IL-6 and TNFa mRNA degradation. Moreover, T0901317 destabilized TNFa mRNA through its 3'-untranslated region. In addition, T0901317 increased the expression of tristetraprolin (TTP), while antagonizing TTP with siRNA abrogated T0901317-mediated inflammatory cytokine mRNA decay. Interestingly, T0901317 repressed LPS-induced phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) in THP-1 macrophages. The evidence presented here confirms that LXR activation with T0901317 inhibits the phosphorylation of ERK1/2 and p38 MAPK, likely resulting in the increased expression of TTP and the decay of LPS-induce inflammatory cytokine mRNAs.
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.
摘要：
A Pd(II)-catalyzed ortho-olefination of aromatic acetic esters is described which features with an excellent funcitional group tolerance, good yields, mild reaction conditions, good scalability as well as high chemo- and regio-selectivity.
作者机构：
[杨晓燕] Institute of Biologic Research;[杨晓燕] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang Hunan 421001, China;[殷杰; 谢红艳] Institute of Biologic Research, University of South China, Hengyang Hunan 421001, China;[向琼; 雷小勇; 虞佳] Institute of Pharmacy and Pharmacology, University of South China, Hengyang Hunan 421001, China;[甘润良; 雷小勇] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study
通讯机构：
Cancer Research Institute, University of South China, Hengyang Hunan, China
作者机构：
[Hongtao Qu; Lu He; Hong Liu] Department of Neurosurgery, The First Affiliated Hospital, University of South China, Hengyang 421001, China;[Hong Zhou] Department of Radiology, The First Affiliated Hospital, University of South China, Hengyang 421001, China;[Hong Zhou] 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：
[Hong Liu; Hongtao Qu] 1;1 Department of Neurosurgery, The First Affiliated Hospital , University of South China , Hengyang 421001 , China
关键词：
park2 gene
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@Ovid database begins with the first 1997 issue.
摘要：
LXR α could have the anti-proliferative effect on multiple cancer cells including breast cancer. However, the mechanisms of LXR α regulating the breast cancer cells remain unclear. This study is to investigate the different expression of LXR α, NF-κB p65 and cyclinD1 in the proliferation of human breast cancer cells. At first, LXR α, NF-κB p65 and cyclinD1 expression were detected by immunohistochemical staining in human breast cancer and paired adjacent breast tissues (n=60). As a result, the three kinds of protein were mainly expressed in cell nuclei. Among them, NF-κB p65 and cyclinD1 were higher expressed in breast cancer tissues than in adjacent tissues while LXR α was lower expressed. Then, MTT assay was used to detect the proliferation of MCF-7 cells and Western blot was used to examine the expression of the three kinds of protein. TO901317 (a kind of artificial agonists against LXRs especially for LXR α) could increase LXR α expression, but decrease NF-κB p65 and cyclinD1 expression and suppress the proliferation of MCF-7 cells in a dose-and time-dependent manner (P< 0.05). Finally, the effects of LXR α siRNA and pyrrolidinedithiocarbamic acid (PDTC, an inhibitory of NF-κB) on TO901317 were observed respectively. LXR α siRNA could significantly decrease the up-regulation of LXR α expression and reverse the inhibited effect of TO901317 on cyclinD1 and NF-κB p65 expression and MCF-7 cell proliferation(P < 0.05) while PDTC could strengthen the inhibition of cell proliferation and further down-regulate NF-κB p65 and cyclinD1 expression induced by TO901317 (P< 0.05), but have little effect on LXR α. In a conclusion, the expression of LXR α, NF-κB p65 and cyclinD1 plays an important role in the proliferation of human breast cancer cells, so as to provide a new method for the molecular targeting treatment of breast cancer in the future.
摘要：
DBU-promoted trifluoromethylation of aryl iodides with difluoromethyltriphenylphosphonium bromide (DFPB) in the presence of copper source is described. In this transformation, DBU not only acts as base to deprotonate the difluoromethyl group in DFPB to generate difluoromethylene phosphonium ylide Ph_3P~+CF_2~-,but also converts the difluorocarbene generated from ylide Ph_3P~+CF_2~-- into trifluoromethyl anion, finally resulting in the trifluoromethylation of aryl iodides. The reactions proceeded smoothly to afford expected products in moderate to good yields.
作者机构：
[肖方竹; 何淑雅; 唐艳] Support Discipline Laboratory of National Defence for Biochemistry and Molecular biology, University of South China, Hengyang, 421001, China;[戴益民] The Key Laboratory of Powder and Transport Materials Protection in Hunan Province, College of Chemistry and Chemical Engineering, Changsha University of Science &, Technology, Changsha, 410004, China;[彭国文] School of Resources and Safety Engineering, Central South University, Changsha, 410083, China;[彭国文] School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001, China
通讯机构：
School of Chemistry and Chemical Engineering, University of South China, Hengyang, China
作者机构：
[Zhengming Li; Xiuping Li] Department of Laboratory, Hunan University of Medicine, Huaihua 418000, China;[Xing Li] Basic Medical Sciences, Hunan University of Medicine, Huaihua 418000, China;[Xiaobo Hu; Weidong Yin] Institute of Cardiovascular Disease, Key Laboratory Arteriosclerology of Hunan Province, University of South China, Hengyang 412000, China;[Sujun Zhang] Department of Experimental Animal, University of South China, Hengyang 412000, China;[Moshe Laudon] Neurim Pharmaceuticals Ltd., Tel-Aviv 69710, Israel
通讯机构：
[Cai, S.] B;Basic Medical Sciences, Hunan University of Medicine, Huaihua, China
关键词：
胰岛素抵抗;调控作用;信号通路;2型糖尿病;分泌能力;患病率;高血糖;细胞
摘要：
The prevalence of Type 2 diabetes (T2D) has been globally increased since the last decade. T2D is a condition of relative insulin insufficiency, in which hyperglycemia develops when the insulin secretory capacity of β-cells is no longer sufficient to meet the insulin requirement in the setting of insulin resistance. Previous studies have shown that there is a close correlation between T2D and insulin receptor substrate-1 (IRS-1) levels, and that lack of expression or abnormal phosphorylation of IRS-1 can lead to insulin resistance. Phosphoinositide 3-kinase (PI3K) plays a key role in insulin signaling and its activity has been shown to be blunted in tissues from T2D subjects. PI3K activation is critical for insulin-mediated metabolic effects such as increased glucose uptake and glycogen synthesis. Glycogen synthase kinase-3β (GSK3β), a downstream target of insulin signaling, is activated by phosphorylated (p) Akt. Phosphorylation by p-Akt inhibits the activity of GSK3β. GSK3β phosphorylation and inactivation are considered to be important mechanisms of cell survival. Melatonin (Mel) is a circulating hormone that is predominantly released from the pineal gland. Some studies suggest that Mel may potentially play a role in diabetes and its associated metabolic disturbances by regulating insulin secretion. Luzindole is a nonspecific Mel receptor antagonist that can block some Mel functions. Although Mel has an extensive range of biological effects, studies have revealed that it is rapidly metabolized with a half-life of 20–30 min once it gets ingested in humans. Therefore, the effect of Mel cannot be studied from direct administration of this drug. Moreover, extraction and synthesis of Mel is complicated and a high dose of Mel is associated with side effects. Neu-P11 is a novel type of nonselective agonist of Mel. It has several characteristics including the ease with which it can be synthesized in vitro and administered effectively for a longer time with fewer side effects. It can also substitute for Mel to interact with its receptors and consequently has an extensive range of biological actions.
作者机构：
Institute of Cardiovascular Disease, University of South China, Key Laboratory for Arteriosclerology of Hunan Province;[Li Lanfang] Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study;[Li Lanfang; Xu Jin; Chen Linxi] Hunan Province Learning Key Laboratory for Pharmacoproteomics, Hengyang, 421001;Institute of Pharmacy and Pharmacology, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study;Institute of Cardiovascular Disease, University of South China, Key Laboratory for Arteriosclerology of Hunan Province, Hengyang, 421001
通讯机构：
[Chen, L.] H
关键词：
Receptor-mediated;reticulophagy;diseases
摘要：
Autophagy is a highly conserved self-digestion process raging from lower eukaryotes to mammals. Autophagy involves in the degradation of misfolded protein aggregates and damaged organelles, which are subsequently reused. Upon autophagy is initiated, a membrane structure termed the phagophore, the precursor of autophagosome, gradually expands and engulfs misfolded protein or damaged organelles and delivers them to the vacuole/lysosome for degradation. Autophagy contributes to the process of survival and death. Basic autophagy is essential for maintaining cellular homeostasis. During normal physiology, specialized cellular function requires the regulation of autophagy by scavenging misfolded protein or damaged organelles. However, excessive and dysregulated autophagy may induce apoptosis and even cell death due to enzymes leaking from lysosomes [1].
作者机构：
[Chen, Lin-xi; Liu, Mei-qing; Chen, Zhe] Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
通讯机构：
[Chen, Lin-xi] U;Univ South China, Inst Pharm & Pharmacol, Hengyang 421001, Peoples R China.
关键词：
endoplasmic reticulum stress;unfolded protein response;ischemic cardiomyopathy;atherosclerosis;hypertension;cardiac hypertrophy;heart failure
摘要：
Endoplasmic reticulum is a principal organelle responsible for folding, post-translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS.
作者机构：
[潘霞; 管馨馨; 黄楠; 张建华; 刘柳成; 张思; 臧婧蕾] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421000, China;[雷小勇] Institute of Pharmacy and Pharmacology, University of South China, Hengyang 421000, China. 1622214323@qq.com
