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Bcl-2 family proteins

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https://www.readbyqxmd.com/read/29156797/jq1-synergizes-with-the-bcl-2-inhibitor-abt-263-against-mycn-amplified-small-cell-lung-cancer
#1
Huogang Wang, Bo Hong, Xuemin Li, Ke Deng, Hong Li, Vivian Wai Yan Lui, Wenchu Lin
Small cell lung cancer (SCLC) is a clinically aggressive cancer with very poor prognosis. Amplification of MYC family genes and overexpression of Bcl-2 protein are common in SCLC, and they are likely therapeutic targets for SCLC. Previous clinical study showed that single agent targeting Bcl-2 with ABT-263 was of limited efficacy in SCLC. In this study, we demonstrated for the first time that co-targeting of N-Myc and Bcl-2 resulted in marked synergistic antitumor effects in MYCN-amplified SCLC. We found that MYCN-amplified SCLC cells were highly sensitive to a Bromodomain and Extra-Terminal domain (BET) inhibitor JQ1, which was able to inhibit N-Myc protein expression...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156771/novel-post-transcriptional-and-post-translational-regulation-of-pro-apoptotic-protein-bok-and-anti-apoptotic-protein-mcl-1-determine-the-fate-of-breast-cancer-cells-to-survive-or-die
#2
Benjamin Onyeagucha, Panneerdoss Subbarayalu, Nourhan Abdelfattah, Subapriya Rajamanickam, Santosh Timilsina, Rosa Guzman, Carla Zeballos, Vijay Eedunuri, Sanjay Bansal, Tabrez Mohammad, Yidong Chen, Ratna K Vadlamudi, Manjeet K Rao
Deregulation of apoptosis is central to cancer progression and a major obstacle to effective treatment. The Bcl-2 gene family members play important roles in the regulation of apoptosis and are frequently altered in cancers. One such member is pro-apoptotic protein Bcl-2-related Ovarian Killer (BOK). Despite its critical role in apoptosis, the regulation of BOK expression is poorly understood in cancers. Here, we discovered that miR-296-5p regulates BOK expression by binding to its 3'-UTR in breast cancers...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156292/dietary-luteolin-protects-against-hgcl2-induced-renal-injury-via-activation-of-nrf2-mediated-signaling-in-rat
#3
Xiao Tan, Biying Liu, Jingjing Lu, Siyu Li, Ruiqi Baiyun, Yueying Lv, Qian Lu, Zhigang Zhang
Luteolin (Lut) belongs to the flavonoid family with various beneficial bioactivities. Here, we investigated whether Lut attenuate mercuric chloride (HgCl2)-induced renal injury in rat. We found that oral gavage administration of Lut (80mg/kg) alleviated anemia and renal histology upon HgCl2 treatment (80mg/L). Lut also significantly reduced HgCl2-induced oxidative stress and inflammatory, presenting as the reduced malondialdehyde (MDA) formation, increased glutathione (GSH) level, and inhibited activation of nuclear factor kappa B (NF-κB)...
November 9, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29151958/santamarine-inhibits-nf-%C3%B0%C2%BAb-and-stat3-activation-and-induces-apoptosis-in-hepg2-liver-cancer-cells-via-oxidative-stress
#4
Tahir Mehmood, Amara Maryam, Xiangge Tian, Muhammad Khan, Tonghui Ma
Sesquiterpene lactones have long been used in traditional Chinese medicines to treat inflammatory diseases. Recently, sesquiterpene lactone family compounds have been recognized as potential anticancer agents. Thus, it is necessary to explore new sesquiterpene lactones and their antitumor mechanism for cancer treatments. In the present study, we have explored the potential anti-cancer activity of a novel sesquiterpene lactone compound "santamarine" (STM) in HepG2 cells. It inhibited proliferation and induced apoptosis dose-dependently with IC50 ~ 70 μM...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29150439/suppression-of-fip200-and-autophagy-by-tumor-derived-lactate-promotes-na%C3%A3-ve-t-cell-apoptosis-and-affects-tumor-immunity
#5
Houjun Xia, Wei Wang, Joel Crespo, Ilona Kryczek, Wei Li, Shuang Wei, Zhaoqun Bian, Tomasz Maj, Mingxiao He, Rebecca J Liu, Youwen He, Ramandeep Rattan, Adnan Munkarah, Jun-Lin Guan, Weiping Zou
Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene Bak1 Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity...
November 17, 2017: Science Immunology
https://www.readbyqxmd.com/read/29149414/role-of-tctp-for-cellular-differentiation-and-cancer-therapy
#6
Ean-Jeong Seo, Nicolas Fischer, Thomas Efferth
The translationally controlled tumor protein (TCTP) is a highly conserved protein that is regulated due to a high number of extracellular stimuli. TCTP has an important role for cell cycle and normal development. On the other side, tumor reversion and malignant transformation have been associated with TCTP. TCTP has been found among the 12 genes that are differentially expressed during mouse oocyte maturation, and an overexpression of this gene was reported in a wide variety of different cancer types. Its antiapoptotic effect is indicated by the interaction with several proapoptotic proteins of the Bcl-2 family and the p53 tumor suppressor protein...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29149100/bcl-2-family-proteins-changing-partners-in-the-dance-towards-death
#7
REVIEW
Justin Kale, Elizabeth J Osterlund, David W Andrews
The BCL-2 family of proteins controls cell death primarily by direct binding interactions that regulate mitochondrial outer membrane permeabilization (MOMP) leading to the irreversible release of intermembrane space proteins, subsequent caspase activation and apoptosis. The affinities and relative abundance of the BCL-2 family proteins dictate the predominate interactions between anti-apoptotic and pro-apoptotic BCL-2 family proteins that regulate MOMP. We highlight the core mechanisms of BCL-2 family regulation of MOMP with an emphasis on how the interactions between the BCL-2 family proteins govern cell fate...
November 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29138212/bax-inhibiting-peptide-attenuates-bleomycin-induced-lung-injury-in-mice
#8
Kunihiro Suzuki, Toyoshi Yanagihara, Tetsuya Yokoyama, Takashige Maeyama, Saiko Ogata-Suetsugu, Masako Arimura-Omori, Hironori Mikumo, Naoki Hamada, Eiji Harada, Kazuyoshi Kuwano, Taishi Harada, Yoichi Nakanishi
Rationale: Bax is a pro-apoptotic member of the Bcl-2 family of proteins, and plays a central role in mitochondria-dependent apoptosis. Several lines of evidence have implied that Bax is involved in both epithelial apoptosis and fibroblast proliferation in idiopathic pulmonary fibrosis; however, the mechanisms remain unknown. Bax-inhibiting peptide V5 (BIP-V5) exhibits membrane permeability and inhibits the activation of Bax.Objective: The purpose of this study was to investigate whether the control of Bax activity by BIP-V5 reduces the degree of bleomycin-induced lung injury...
November 14, 2017: Biology Open
https://www.readbyqxmd.com/read/29131417/culturing-with-modified-egm2-medium-enhances-porcine-neonatal-islet-like-cell-clusters-resistance-to-apoptosis-in-islet-xenotransplantation
#9
Xiaoqian Ma, Cejun Yang, Juan Zhang, Jia Wang, Wei Li, Chang Xu, Pengfei Rong, Bin Ye, Minghua Wu, Jianhui Jiang, Shounan Yi, Wei Wang
BACKGROUND: Neonatal pig islet-like cell clusters (NICC) are an attractive source of insulin-producing tissue for potential transplantation treatment of type 1 diabetic patients. However, a considerable loss of NICC after their transplantation due to apoptosis resulted from islet isolation and instant blood-mediated inflammatory reaction remains to be overcome. METHODS: EGM2 medium depleted with hydrocortisone and supplemented with 50 mmol/L isobutylmethylxanthine, 10 mmol/L nicotinamide, and 10 mmol/L glucose was used to culture NICC at day 1, the day after isolation and changed every other day...
November 12, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/29125379/bcl-xl-bak-interaction-and-regulation-by-mirna-let-7b-in-the-intrinsic-apoptotic-pathway-of-stored-platelets
#10
Yuzhong Yan, Rufeng Xie, Qi Zhang, Xinfang Zhu, Jia Han, Rong Xia
Bcl-2 family proteins play key roles in the intrinsic apoptosis pathway in platelets, with both pro- and antiapoptotic protein expressions regulating survival during ex vivo storage. We detected a significant decrease in antiapoptotic Bcl-xL and increase in proapoptotic Bak expression on the third day of storage and as a result the ratio of Bak:Bcl-xL also decreased. Moreover, we identified an interaction between Bcl-xL and Bak. These shifts corresponded with activation of the apoptotic pathway, suggesting these proteins might play an important role in platelet survival...
November 10, 2017: Platelets
https://www.readbyqxmd.com/read/29120799/study-on-the-effect-of-reactive-oxygen-species-mediated-oxidative-stress-on-the-activation-of-mitochondrial-apoptosis-and-the-tenderness-of-yak-meat
#11
Lin-Lin Wang, Qun-Li Yu, Ling Han, Xiu-Li Ma, Ren-De Song, Suo-Nan Zhao, Wen-Hua Zhang
This study investigated the effect of reactive oxygen species-mediated oxidative stress on activation of mitochondrial apoptosis and tenderness of yak meat during postmortem ageing. Oxidative stress degree, Ca(2+) levels, membrane permeability transition pore opening, mitochondrial membrane potential, apoptotic factors and the shear force were examined. Results showed that the ROS generated by H2O2 significantly increased mitochondrial oxidative stress by decreasing the activities of superoxide dismutase, catalase and glutathione peroxidase, and increasing lipid peroxidation...
April 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29115547/preventive-effect-of-hesperidin-modulates-inflammatory-responses-and-antioxidant-status-following-acute-myocardial-infarction-through-the-expression-of-ppar%C3%A2-%C3%AE-and-bcl%C3%A2-2-in-model-mice
#12
Chunying Meng, Zeheng Guo, Dagang Li, Hanwei Li, Jianbin He, Dingguo Wen, Bin Luo
Hesperetin is the main pharmacological ingredient of fruit of the citrus family, rutaceae. It is a flavanone, which has potent antioxidation and anti‑inflammatory activities. The present study investigated the preventive effect of hesperidin in the modulation of acute myocardial infarction (AMI)‑induced inflammatory responses and antioxidant status in a mouse model. The levels of creatine kinase‑MB, tumor necrosis factor (TNF‑α), interleukin (IL)‑1β, IL‑6, monocyte chemoattractant protein 1 (MCP‑1), intercellular adhesion molecule 1 (ICAM‑1), malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) and caspase‑3/9 were measured using ELISA kits...
November 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29114065/bim-suppresses-the-development-of-sle-by-limiting-myeloid-inflammatory-responses
#13
FuNien Tsai, Philip J Homan, Hemant Agrawal, Alexander V Misharin, Hiam Abdala-Valencia, G Kenneth Haines, Salina Dominguez, Christina L Bloomfield, Rana Saber, Anthony Chang, Chandra Mohan, Jack Hutcheson, Anne Davidson, G R Scott Budinger, Philippe Bouillet, Andrea Dorfleutner, Christian Stehlik, Deborah R Winter, Carla M Cuda, Harris Perlman
The Bcl-2 family is considered the guardian of the mitochondrial apoptotic pathway. We demonstrate that Bim acts as a molecular rheostat by controlling macrophage function not only in lymphoid organs but also in end organs, thereby preventing the break in tolerance. Mice lacking Bim in myeloid cells (LysM(Cre)Bim(fl/fl)) develop a systemic lupus erythematosus (SLE)-like disease that mirrors aged Bim(-/-) mice, including loss of marginal zone macrophages, splenomegaly, lymphadenopathy, autoantibodies (including anti-DNA IgG), and a type I interferon signature...
November 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29105957/supplementary-choline-attenuates-olive-oil-lipid-emulsion-induced-enterocyte-apoptosis-through-suppression-of-celf1-aif-pathway
#14
Jun-Kai Yan, Jie Zhu, Zi-Zhen Gong, Jie Wen, Yong-Tao Xiao, Tian Zhang, Wei Cai
Enterocyte apoptosis induced by lipid emulsions is a key cause of intestinal atrophy under total parenteral nutrition (TPN) support, and our previous work demonstrated that olive oil lipid emulsion (OOLE) could induce enterocyte apoptosis via CUGBP, Elav-like family member 1 (CELF1)/ apoptosis-inducing factor (AIF) pathway. As TPN-associated complications are partially related to choline deficiency, we aimed to address whether choline supplementation could attenuate OOLE-induced enterocyte apoptosis. Herein we present evidence that supplementary choline exhibits protective effect against OOLE-induced enterocyte apoptosis both in vivo and in vitro...
November 6, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29104479/knockdown-of-yes-associated-protein-induces-the-apoptosis-while-inhibits-the-proliferation-of-human-periodontal-ligament-stem-cells-through-crosstalk-between-erk-and-bcl-2-signaling-pathways
#15
Yong Wen, Yawen Ji, Yunpeng Zhang, Baoqi Jiang, Cuizhu Tang, Qi Wang, Xiyan Chen, Linglu Jia, Weiting Gu, Xin Xu
Objective: The purpose of this study was to provide an insight into the biological effects of knockdown Yes-associated protein (YAP) on the proliferation and apoptosis of human periodontal ligament stem cells (h-PDLSCs). Methods: Immunofluorescence and Western blot were used to evaluate Hippo-YAP signaling expression level. Enhanced green fluorescence protein lentiviral vector was constructed to down-regulate YAP in h-PDLSCs. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the interfering efficiency of YAP expression...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29100606/bh3-only-protein-bim-an-emerging-target-in-chemotherapy
#16
REVIEW
Shatrunajay Shukla, Sugandh Saxena, Brijesh Kumar Singh, Poonam Kakkar
BH3-only proteins constitute major proportion of pro-apoptotic members of B-cell lymphoma 2 (Bcl-2) family of apoptotic regulatory proteins and participate in embryonic development, tissue homeostasis and immunity. Absence of BH3-only proteins contributes to autoimmune disorders and tumorigenesis. Bim (Bcl-2 Interacting Mediator of cell death), most important member of BH3-only proteins, shares a BH3-only domain (9-16 aa) among 4 domains (BH1-BH4) of Bcl-2 family proteins and highly pro-apoptotic in nature...
December 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/29099483/the-bcl-2-arbiters-of-apoptosis-and-their-growing-role-as-cancer-targets
#17
REVIEW
Jerry M Adams, Suzanne Cory
Impaired apoptosis plays a central role in cancer development and limits the efficacy of conventional cytotoxic therapies. Deepening understanding of how opposing factions of the BCL-2 protein family switch on apoptosis and of their structures has driven development of a new class of cancer drugs that targets various pro-survival members by mimicking their natural inhibitors, the BH3-only proteins. These 'BH3 mimetic' drugs seem destined to become powerful new weapons in the arsenal against cancer. Successful clinical trials of venetoclax/ABT-199, a specific inhibitor of BCL-2, have led to its approval for a refractory form of chronic lymphocytic leukaemia and to scores of on-going trials for other malignancies...
November 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29097252/nf-%C3%AE%C2%BAb-and-jnk-mediated-apoptosis-and-g0-g1-arrest-of-hela-cells-induced-by-rubiarbonol-g-an-arborinane-type-triterpenoid-from-rubia-yunnanensis
#18
Guang-Zhi Zeng, Zhe Wang, Li-Mei Zhao, Jun-Ting Fan, Ning-Hua Tan
ETHNOPHARMACOLOGICAL RELEVANCE: Rubia yunnanensis is a medicinal plant mainly grown in Yunnan province in Southwest China, and its root named "Xiaohongshen" has been used as a herb in Yunnan for the treatment of cancers. Three major types of chemical components, Rubiaceae-type cyclopeptides, quinones, and triterpenoids, were identified from R. yunnanensis, in which some of compounds including rubiarbonol G (RG), a unique arboriane-type triterpenoid, showed cytotoxicity on cancer cells...
October 30, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29096158/human-hepatocytes-apoptosis-induced-by-replication-of-hepatitis-b-virus-subgenotypes-f1b-and-f4-role-of-basal-core-promoter-and-precore-mutations
#19
María Mercedes Elizalde, Ina Sevic, María Mora González López Ledesma, Rodolfo Héctor Campos, Luciana Barbini, Diego Martin Flichman
In the context of pathogenesis of HBV infection, HBV genotypes and mutants have been shown to affect the natural course of chronic infection and treatment outcomes. In this work, we studied the induction of apoptosis by the replication of HBV subgenotypes F1b and F4, and the naturally occurring mutants BCP and preCore. Both subgenotypes F1b and F4 HBV genome transfections induced cell death by apoptosis in human hepatocytes. The BCPdm (A1762T/G1764A) and preCore (G1896A) mutants induced higher levels of apoptosis than the wt virus...
October 27, 2017: Virology
https://www.readbyqxmd.com/read/29089868/chl1-is-expressed-and-functions-as-a-malignancy-promoter-in-glioma-cells
#20
Zhai Yang, Qing Xie, Cheng-Liang Hu, Qiong Jiang, Hui-Fan Shen, Melitta Schachner, Wei-Jiang Zhao
The cell adhesion molecule with homology to L1CAM (close homolog of L1) (CHL1) is a member of the cell adhesion molecule L1 (L1CAM) gene family. Although CHL1 expression and function have been reported in several tumors, the roles of CHL1 in the development of glioma remain unclear. In the present study, we investigated the effects of CHL1 on proliferation indexes and activation of Akt1 and Erk signaling by siRNA in U-87 MG human glioblastoma and human U251 and SHG-44 glioma cells. We found that siRNA targeting CHL1 significantly down-regulated the expression of CHL1 mRNA and protein accompanied by reduced cell proliferation and transmigration invasion in all three cell lines...
2017: Frontiers in Molecular Neuroscience
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