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Bcl-2 family proteins

Shi-Yun Jin, Jun Huang, Hai-Juan Zhu, Hao Wu, Shi-Jin Xu, Michael G Irwin, Shu-Fang He, Ye Zhang
Remifentanil preconditioning (RPC) exerts protection in normal hearts, but has not been investigated in heart failure. The aim of the present study was to evaluate the effect of RPC in a chronic failing rat heart model and the mechanisms involving mitogen-activated protein kinases (MAPK) and Bcl-2 protein family. The doxorubicin induced failing rat hearts were subjected to 30min ischemia / 120min reperfusion (IR) with or without RPC by using Langendorff apparatus. RPC was induced by three cycles of 5min remifentanil / 5min drug-free perfusion before IR, with three different concentrations: 25, 50 and 100μg/l...
March 17, 2018: European Journal of Pharmacology
Wei Chen, Xiaoqun Liu, Sujuan Yuan, Tiankui Qiao
Although cisplatin (CDDP) is widely used for non-small-cell lung cancer (NSCLC) treatment, resistance remains a major problem that restricts its efficacy. Therefore, identification of drugs that reverse or prevent resistance to CDDP in NSCLC has been a focus of a number of studies. The results of the present study revealed the effect of heat shock protein family A member 12B (HSPA12B) overexpression on chemoresistance in A549 cells in vitro . The effect of HSPA12B overexpression on chemoresistance in mice bearing A549 xenografted tumors was then determined via stable HSPA12B transfection...
March 2018: Oncology Letters
Yibin Hao, Jianhua Zhang, Guoyong Shan, Ning Zhang, Wenwen Jin, Kejun Nan
Objective: to establish regulatory network of colorectal cancer involving p42.3 protein and to provide theoretical evidence for deep functional exploration of p42.3 protein in the onset and development of colorectal cancer. Methods: with protein similarity algorithm, reference protein set of p42.3 cell apoptosis was built according to structural features of p42.3. GO and KEGG databases were used to establish regulatory network of tumor cell apoptosis involving p42.3; meanwhile, the largest possible working pathway that involves p42...
December 2017: Saudi Journal of Biological Sciences
Lu Sun, Zheng-Guo Cui, Shahbaz Ahmad Zakki, Qian-Wen Feng, Meng-Ling Li, Hidekuni Inadera
Hyperthermia is one therapeutic tool for damaging and killing cancer cells, with minimal injury to normal tissues. However, its cytotoxic effects alone are insufficient for quantitative cancer cell death. To overcome this limitation, several studies have explored non-toxic enhancers for hyperthermia-induced cell death. Capsaicin may be applicable as a therapeutic tool against various types of cancer. In the present study, we employed nonivamide, a less-pungent capsaicin analogue, to investigate its possible enhancing effects on hyperthermia-induced apoptosis; moreover, we analyzed its molecular mechanism...
March 15, 2018: Free Radical Biology & Medicine
Chengzheng Han, Guozheng Xing, Mengying Zhang, Min Zhong, Zhen Han, Chiyi He, Xiaoping Liu
Wogonoside, the main effective constituent of traditional Chinese medicine Scutellaria , belongs to the glucuronide family, with various functions, including detoxification, anti-inflammation and nourishing gallbladder, lowering blood pressure, diuresis and anti-allergic reactions. However, the effects of wogonoside on human colon cancer cells remain unclear. The present study aimed to investigate the anticancer effect of wogonoside on human colon cancer cells in vitro and its anticancer mechanisms. The results demonstrated that wogonoside significantly inhibited cell growth, induced apoptosis and mitochondrial-mediated autophagy of colon cancer cells...
April 2018: Oncology Letters
Aleksandra Pawlak, Witold Gładkowski, Justyna Kutkowska, Marcelina Mazur, Bożena Obmińska-Mrukowicz, Andrzej Rapak
For many years, studies focused on developing new natural or synthetic compounds with antineoplastic activity have attracted the attention of researchers. An interesting group of such compounds seem to be those with both lactone moiety and an aromatic ring which, in addition to antimicrobial or antiviral activity, also exhibit antitumor properties. The study shows antitumor activity of two enantiomeric trans isomers of 5-(1-iodoethyl)-4-(2',5'-dimethylphenyl)dihydrofuran-2-one. Our aim was to determine their antitumor activity manifested as an ability to induce apoptosis in selected canine cancer cell lines as well as to evaluate differences in their strength depending on the configuration of their stereogenic centers...
March 3, 2018: Bioorganic & Medicinal Chemistry Letters
Haiting Chen, Huifang Wang, Jianbin An, Qingli Shang, Jingxue Ma
BACKGROUND: This study aimed to explore the effects of plumbagin (PLB) on ARPE-19 cells and underlying mechanism. METHODS: Cultured ARPE-19 cells were treated with various concentrations (0, 5, 15, and 25 μM) of PLB for 24 h or with 15 μM PLB for 12, 24 and 48 h. Then cell viability was evaluated by MTT assay and DAPI staining, while apoptosis and cell cycle progression of ARPE cells were assessed by flow cytometric analysis. Furthermore, the level of main regulatory proteins was examinated by Western boltting and the expression of relative mRNA was tested by Real-Time PCR...
March 13, 2018: BMC Complementary and Alternative Medicine
Yanwu Hu, Haitao Li, Kai Liu, Yang Zhang, Liqun Ren, Zhimin Fan
Icariin belongs to the family of flavonoids that is extracted from Epimedium brevicornum Maxim, and exhibits antioxidative, antitumorigenic, antiosteoporotic, immunoregulatory and antiatherosclerotic properties. To understand the mechanisms underlying the antiatherosclerotic properties of icariin, the present study investigated the effects of icariin on human vascular endothelial cells (HUVECs) following treatment with oxidized low‑density lipoprotein (ox‑LDL). Thus, following pretreatment with icariin at four various concentrations (0, 10, 20 and 40 µM), HUVECs were stimulated with ox‑LDL (100 µg/ml)...
March 9, 2018: Molecular Medicine Reports
Sei Kuriyama, Tadahiro Tsuji, Tetsushi Sakuma, Takashi Yamamoto, Masamistu Tanaka
The anti-apoptotic nature of cancer cells often impedes the effects of anti-cancer therapeutic agents. Multiple death signals influence mitochondria during apoptosis, and though many studies have attempted to elucidate these complicated pathways, Bax oligomerization, an important step in the process, remains controversial. Here we demonstrate that pleckstrin-homology N1 (PLEKHN1), also known as cardiolipin phosphatidic acid binding protein, plays pro-apoptotic roles during reactive oxygen species (ROS)-induced apoptosis...
December 2018: Cell Death Discovery
Ye-Fen Lu, Xue-Li Cai, Zheng-Zheng Li, Jing Lv, Yi-An Xiang, Jian-Jun Chen, Wei-Jing Chen, Wei-Yan Sun, Xiu-Mei Liu, Jian-Bo Chen
BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. METHODS: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed...
March 6, 2018: Cellular Physiology and Biochemistry
Yan Xia, Axel W Fischer, Pedro Teixeira, Brian Weiner, Jens Meiler
While great progress has been made, only 10% of the nearly 1,000 integral, α-helical, multi-span membrane protein families are represented by at least one experimentally determined structure in the PDB. Previously, we developed the algorithm BCL::MP-Fold, which samples the large conformational space of membrane proteins de novo by assembling predicted secondary structure elements guided by knowledge-based potentials. Here, we present a case study of rhodopsin fold determination by integrating sparse and/or low-resolution restraints from multiple experimental techniques including electron microscopy, electron paramagnetic resonance spectroscopy, and nuclear magnetic resonance spectroscopy...
February 23, 2018: Structure
Mark Yulis, Miguel Quiros, Roland Hilgarth, Charles A Parkos, Asma Nusrat
Desmosomal cadherins mediate intercellular adhesion and have also been shown to regulate homeostatic signaling in epithelial cells. We have previously reported that select pro-inflammatory cytokines induce Dsg2 ectodomain cleavage and shedding from intestinal epithelial cells (IECs). Dsg2 extracellular cleaved fragments (Dsg2 ECF) function to induce paracrine pro-proliferative signaling in epithelial cells. In this study, we show that exposure of IECs to pro-inflammatory cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) resulted in Dsg2 intracellular cleavage and generation of a ~55 kDa fragment (Dsg2 ICF)...
March 9, 2018: Cell Death & Disease
Rami Z Morsi, Rouba Hage-Sleiman, Hadile Kobeissy, Ghassan Dbaibo
The B-cell lymphoma 2 (Bcl-2) family proteins play an important role in regulating apoptosis, or programmed cell death, in response to several extracellular and intracellular signals. These proteins are either pro-apoptotic or anti-apoptotic. The pro-apoptotic Noxa is a Bcl-2 family protein that belongs to a subclass of BH3-only proteins. Noxa induces apoptosis via p53-dependent and/or p53-independent mechanisms. While Noxa may play a limited role in apoptosis, it is a crucial player that interacts with several proteins in the apoptosis pathway, highlighting its importance in the pathogenesis and treatment of certain cancers...
March 7, 2018: Current Cancer Drug Targets
Nadia Khan, Brad Kahl
Resistance to apoptosis is one of the hallmarks of cancer and members of the B-cell lymphoma 2 (BCL-2) family of proteins are central regulators of apoptosis. Many cancers become resistant to chemotherapy and apoptosis by up-regulating BCL-2 and other family members, making these proteins attractive targets for cancer therapy. Venetoclax is an orally administered, small-molecule apoptosis stimulant that targets BCL-2 proteins by acting as a BCL-2 homology domain 3 (BH3) mimetic. The drug is approved in the USA and EU as a monotherapy for the for the treatment of certain patients with chronic lymphocytic leukemia (CLL) and is in phase III clinical development for multiple myeloma (MM), and in phase II or I/II clinical trials for acute myeloid leukemia, and several B-cell malignancies, including diffuse large B-cell lymphoma, Waldenstrom's macroglobulinaemia, follicular lymphoma, and mantle-cell lymphoma...
March 8, 2018: Targeted Oncology
Zhi-Chuan Zhu, Ji-Wei Liu, Kui Li, Jing Zheng, Zhi-Qi Xiong
The nuclear import receptor karyopherin β1 (KPNB1) is involved in the nuclear import of most proteins and in the regulation of multiple mitotic events. Upregulation of KPNB1 has been observed in cancers including glioblastoma. Depletion of KPNB1 induces mitotic arrest and apoptosis in cancer cells, but the underlying mechanism is not clearly elucidated. Here, we found that downregulation and functional inhibition of KPNB1 in glioblastoma cells induced growth arrest and apoptosis without apparent mitotic arrest...
March 9, 2018: Oncogene
Hong-Qiang Chen, Ji Zhao, Yan Li, Li-Xiong He, Yu-Jing Huang, Wei-Qun Shu, Jia Cao, Wen-Bin Liu, Jin-Yi Liu
Microcystin (MC) is a cyclic heptapeptide compound which could lead to the development of hepatocellular carcinoma. However, the underlying epigenetic regulation mechanism is largely unknown. In this study, microcystin-LR (L: lysine, R: arginine, MC-LR) was used to induce the malignant transformation of human hepatocyte L02 cell line. The profile of gene expression, microRNA (miRNA) and DNA methylation were detected through high-throughput sequencing. Compared with control group, the expression of 826 genes and 187 miRNAs changed significantly in MC-LR treated group...
March 5, 2018: Toxicology Letters
Emma Mattsson, Peter Saliba-Gustafsson, Ewa Ehrenborg, Per Tornvall
BACKGROUND: Takotsubo cardiomyopathy (TCM), also known as "broken heart syndrome", is a type of heart failure characterized by transient ventricular dysfunction in the absence of obstructive coronary lesions. Although associated with increased levels of catecholamines, pathophysiological mechanisms are unknown. Relapses and family heritability indicate a genetic predisposition. Several small studies have investigated associations between three different loci; the β1-adrenic receptor (ADRB1), G-protein-coupled receptor kinase 5 (GRK5), Bcl-associated athanogene 3 (BAG3) and TCM but no consensus has been reached...
March 7, 2018: BMC Medical Genetics
Le Yang, Yong-Song Cai, Ke Xu, Jia-Lin Zhu, Yuan-Bo Li, Xiao-Qing Wu, Jian Sun, She-Min Lu, Peng Xu
The present study aimed to examine the effects of sodium selenite on the SW982 human synovial sarcoma cell line in relation to cell viability, apoptosis and autophagy. The results indicated that sodium selenite reduced cell viability and induced apoptosis by activating caspase‑3 and members of the poly (ADP‑ribose) polymerase and Bcl‑2 protein families in SW982 cells. Furthermore, autophagy was also suppressed by sodium selenite treatment in SW982 cells, and apoptosis was upregulated in cells co‑treated with sodium selenite and the autophagy inhibitor 3‑methyladenine...
March 6, 2018: Molecular Medicine Reports
Yanfang Wu, Xia Li, Junying Jia, Yanpeng Zhang, Jing Li, Zhengmao Zhu, Huaqing Wang, Jie Tang, Junjie Hu
The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and triggers the unfolded protein response (UPR). Failure to resolve ER stress leads to apoptotic cell death via a yet unclear mechanism. Here, we show that RNF183, a membrane-spanning RING finger protein, localizes to the ER and exhibits classic E3 ligase activities. Sustained ER stress induced by different treatments increases RNF183 protein levels posttranscriptionally in an IRE1α-dependent manner. Activated IRE1 reduces the level of miR-7, which increases the stability of RNF183 transcripts...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Silvia Escudero, Elma Zaganjor, Susan Lee, Christopher P Mill, Ann M Morgan, Emily B Crawford, Jiahao Chen, Thomas E Wales, Rida Mourtada, James Luccarelli, Gregory H Bird, Ulrich Steidl, John R Engen, Marcia C Haigis, Joseph T Opferman, Loren D Walensky
MCL-1 is a BCL-2 family protein implicated in the development and chemoresistance of human cancer. Unlike its anti-apoptotic homologs, Mcl-1 deletion has profound physiologic consequences, indicative of a broader role in homeostasis. We report that the BCL-2 homology 3 (BH3) α helix of MCL-1 can directly engage very long-chain acyl-CoA dehydrogenase (VLCAD), a key enzyme of the mitochondrial fatty acid β-oxidation (FAO) pathway. Proteomic analysis confirmed that the mitochondrial matrix isoform of MCL-1 (MCL-1Matrix ) interacts with VLCAD...
March 1, 2018: Molecular Cell
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