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bcl2 family

Haibo Huang, Qianqian Geng, Hong Yao, Zhenhuang Shen, Zhenhong Wu, Xiaoqing Miao, Peiying Shi
Objectives: Scutellarin ( Scu ) is the main effective constituent of Erigeron breviscapus which has anti-oxidant, anti-apoptotic, anti-inflammatory and other therapeutic properties. The purpose of this study was to investigate the protective effect of Scu on myocardial infarction (MI) induced by isoprenaline (ISO). Materials and Methods: The rats were subcutaneously injected with ISO (45 mg/kg) on the first day, then single tail-intravenously injected with different doses of Scu (10 mg/kg, 20 mg/kg, 40 mg/kg) for 7 consecutive days...
March 2018: Iranian Journal of Basic Medical Sciences
Thomas Patzelt, Selina J Keppler, Oliver Gorka, Silvia Thoene, Tim Wartewig, Michael Reth, Irmgard Förster, Roland Lang, Maike Buchner, Jürgen Ruland
The transcription factor Foxp1 is critical for early B cell development. Despite frequent deregulation of Foxp1 in B cell lymphoma, the physiological functions of Foxp1 in mature B cells remain unknown. Here, we used conditional gene targeting in the B cell lineage and report that Foxp1 disruption in developing and mature B cells results in reduced numbers and frequencies of follicular and B-1 B cells and in impaired antibody production upon T cell-independent immunization in vivo. Moreover, Foxp1 -deficient B cells are impaired in survival even though they exhibit an increased capacity to proliferate...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Selma Tuzlak, Manuel D Haschka, Anna-Maria Mokina, Thomas Rülicke, Suzanne Cory, Verena Labi, Andreas Villunger
Overexpression of BCLX and BFL1/A1 has been reported in various human malignancies and is associated with poor prognosis and drug-resistance, identifying these pro-survival BCL2 family members as putative drug-targets. We have generated transgenic mice that express human BFL1 or human BCLX protein throughout the hematopoietic system under the control of the Vav-gene promoter. Hematopoiesis is normal in both the Vav-BFL1 and Vav-BCLX transgenic (TG) mice and susceptibility to spontaneous hematopoietic malignancies is not increased...
March 2, 2018: FEBS Journal
Yi Yang, Woo Kyun Bae, Sang-Jip Nam, Min-Hye Jeong, Rui Zhou, So-Yeon Park, İsa Taş, Yun-Ho Hwang, Myong-Suk Park, Ik Joo Chung, Kyung Keun Kim, Jae-Seoun Hur, Hangun Kim
BACKGROUND: Endolichenic fungi are microbes that inhabit the thalli of lichens and produce various unique chemicals that can be used for pharmaceutical purposes. PURPOSE: This study screened a library of endolichenic fungal extracts to identify novel anticancer agents capable of suppressing the tumorigenicity of human cancer cells. METHODS: Active compounds were isolated from extracts of endolichenic fungi by column chromatography and reverse-phase HPLC...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Zhenzhen Zhang, Song Wu, Saeed Muhammad, Qian Ren, Chao Sun
Both miR-103 and 107 have been demonstrated to restrain cell proliferation, regulate lipid metabolism and inflammation. However, the effects of miR-103/107 on preadipocytes apoptosis remain unknown. In the present research, we have investigated how miR-103/107 regulated preadipocytes apoptosis. We found that miR-103/107 aggravated Endoplasmic Reticulum (ER) stress mediated apoptosis in preadipocytes. We confirmed that miR-103/107 targeted Wnt3a (WNT family member 3a) in preadipocytes. It was found that overexpressing Wnt3a resulted in suppression of ER stress mediated apoptosis, while restoration of miR-103/107 counteracted the effects of Wnt3a in preadipocytes...
February 26, 2018: Journal of Lipid Research
Suresh Banjara, Jiahao Mao, Timothy M Ryan, Sofia Caria, Marc Kvansakul
Programmed cell death or apoptosis is a critical mechanism for the controlled removal of damaged or infected cells, and proteins of the BCL-2 family are important arbiters of this process. Viruses have been shown to encode functional and structural homologs of BCL-2 to counter premature host-cell apoptosis and ensure viral proliferation or survival. Grouper iridovirus (GIV) is a large DNA virus belonging to the Iridoviridae family and harbors GIV66, a putative BCL-2 like protein and mitochondrially localized apoptosis inhibitor...
February 26, 2018: Journal of Biological Chemistry
Jana Mihalyova, Tomas Jelinek, Katerina Growkova, Matous Hrdinka, Michal Simicek, Roman Hajek
Inhibitors of anti-apoptotic proteins of the BCL2 family can successfully restart the deregulated process of apoptosis in malignant cells. While non-selective agents have been limited by their affinity to different BCL2 members, and thus inducing excessive toxicity, the highly selective BCL2 inhibitor, venetoclax (ABT-199, Venclexta™), has an acceptable safety profile. To date, it has been approved in monotherapy for the treatment of relapsed or refractory chronic lymphocytic leukaemia (CLL) with 17p deletion...
February 22, 2018: Experimental Hematology
J Malcikova, E Tausch, D Rossi, L A Sutton, T Soussi, T Zenz, A P Kater, C U Niemann, D Gonzalez, F Davi, M Gonzalez Diaz, C Moreno, G Gaidano, K Stamatopoulos, R Rosenquist, S Stilgenbauer, P Ghia, S Pospisilova
In chronic lymphocytic leukemia (CLL), TP53 gene defects, due to deletion of the 17p13 locus and/or mutation(s) within the TP53 gene, are associated with resistance to chemoimmunotherapy and a particularly dismal clinical outcome. On these grounds, analysis of TP53 aberrations has been incorporated into routine clinical diagnostics to improve patient stratification and optimize therapeutic decisions. The predictive implications of TP53 aberrations have increasing significance in the era of novel targeted therapies, i...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Elnaz Hajipour, Farideh Jalali Mashayekhi, Ghasem Mosayebi, Maryam Baazm, Adib Zendedel
Objectives: Varicocele is an abnormal dilation in the testicular vein, which can cause hypoxia, reactive oxygen species accumulation, elevation in testicular temperature, and promote apoptosis and increase proinflammatory cytokine production. According to the varicocele pathophysiology, it is possible that a group of cytosolic receptors called nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes also involve in varicocele pathogenesis...
February 2018: Iranian Journal of Basic Medical Sciences
Aneta A Koronowicz, Mariola Drozdowska, Barbara Wielgos, Ewelina Piasna-Słupecka, Dominik Domagała, Joanna Dulińska-Litewka, Teresa Leszczyńska
NutramilTM Complex is a multicomponent food product that meets the requirements of a food for special medical purpose. As a complete, high-energy diet it consists of properly balanced nutrients, vitamins and minerals. The aim of this study was to assess the effect of NutramilTM Complex on breast and prostate carcinoma cells. Our results showed that NutramilTM Complex reduced the viability and proliferation of breast and prostate cancer cells and that this process was associated with the induction of apoptosis via activation of caspase signalling...
2018: PloS One
Xue Guan, Shuo Chen, Yao Liu, Li-Li Wang, Yang Zhao, Zhi-Hong Zong
BACKGROUND: Abnormal expression of the PUM1 gene (pumilio RNA binding family member 1) is closely related to chromosomal mutations and carcinogenesis. However, there is no report about expression or function of PUM1 in ovarian cancer. The present study explored the role of PUM1 in the development and progression of ovarian cancer. METHODS: Immunohistochemistry was used to detect the expression of PUM1 in normal ovarian tissues and ovarian cancer tissues. The PUM1 gene was silenced using small interfering RNAs in ovarian cancer cell line A2780...
February 8, 2018: Biochemical and Biophysical Research Communications
Hio Teng Cheong, Fei Xu, Chi Tung Choy, Connie Wun Chun Hui, Tony Shu Kam Mok, Chi Hang Wong
Lung cancer has the highest incidence and mortality rate worldwide among all malignancy-associated mortalities, of which non-small cell lung cancer accounts for 80% of all cases. Resistance against epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) develops following 8-12 months of disease progression, and is a critical issue. HCC827 cell lines with resistance to EGFR-TKIs were successfully screened. The half maximal inhibitory concentration values were 1,000-fold higher than the values for the parental HCC827 cell line, thereby demonstrating cross-resistance against the same family of TKIs...
January 2018: Oncology Letters
Gerard Nuovo, Vicky Amann, James Williams, Paige Vandiver, Maria Quinonez, Paolo Fadda, Bernard Paniccia, Louisa Mezache, Adel Mikhail
Understanding the metabolic profile of neurons with the hyperphosphorylated tau protein characteristic of Alzheimer's disease is essential to unraveling new potential therapies and diagnostics for the surgical pathologist. We stratified 75 brain tissues from Alzheimer's disease into hyperphosphorylated tau positive or negative and did co-expression analyses and qRTPCR for importin-β and exportin-5 plus several bcl2 family members and compared the data to controls, Down's dementia and Parkinson's disease. There was a significant increase in the expression of importin-β and exportin-5 in Alzheimer's disease relative to the three other categories (each p value<0...
February 2018: Annals of Diagnostic Pathology
Ayano Kabashima, Petra Hirsova, Steven F Bronk, Matthew C Hernandez, Mark J Truty, Sumera Rizvi, Scott H Kaufmann, Gregory J Gores
BACKGROUND & AIMS: Myeloid cell leukemia1 (MCL1), a prosurvival member of the BCL2 protein family, plays a pivotal role in human cholangiocarcinoma (CCA) cell survival. We have previously reported that fibroblast growth factor receptor (FGFR) signaling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. METHODS: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays...
February 2, 2018: Journal of Hepatology
Rathinavel Ashokkumar, Sankar Jamuna, M S Sakeena Sadullah, S Niranjali Devaraj
The molecular mechanisms involved in ER stress-induced post myocardial injury remain elusive. In this study, we have investigated the molecular mechanism of ER stress-mediated myocyte death in Isoproterenol (ISO) induced myocardial infarction and its inhibition by a potent anti oxidant and anti-apoptotic bioflavonoid, Vitexin. ISO mediated apoptosis was found to be associated with ER permeabilization and characterized by enhanced production of ROS, activation of caspase-3, modulation of Bcl2 family proteins and activation of bnip3...
February 5, 2018: Biochemical and Biophysical Research Communications
Solenn M Guilbert, Herman Lambert, Marc-Antoine Rodrigue, Margit Fuchs, Jacques Landry, Josée N Lavoie
BCL2-associated athanogene (BAG)-3 is viewed as a platform that would physically and functionally link distinct classes of molecular chaperones of the heat shock protein (HSP) family for the stabilization and clearance of damaged proteins. In this study, we show that HSPB8, a member of the small heat shock protein subfamily, cooperates with BAG3 to coordinate the sequestration of harmful proteins and the cellular adaptive response upon proteasome inhibition. Silencing of HSPB8, like depletion of BAG3, inhibited targeting of ubiquitinated proteins to the juxtanuclear aggresome, a mammalian system of spatial quality control...
February 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Candela R González, María L Muscarsel Isla, Alfredo D Vitullo
Mammalian testis undergoes deep changes in their architecture and function during photoregression conditions in seasonal breeders. Particularly, the testicular mechanisms that regulate the transition between the active (functional) and inactive (regression) stage vary between species. The aim of the present study was to analyze the incidence of proliferation, apoptosis and autophagy in the testicular seminiferous ephitelium of a seasonal breeder, Lagostomus maximus, during the annual reproductive cycle. We observed that proliferating spermatogonia increased from the active testis until reaching the maximum peak in the activating testis...
2018: PloS One
Santiago Lima, Kazuaki Takabe, Jason Newton, Kumar Saurabh, Megan M Young, Andreia Machado Leopoldino, Nitai C Hait, Jane L Roberts, Hong-Gang Wang, Paul Dent, Sheldon Milstien, Laurence Booth, Sarah Spiegel
The bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P) and the enzyme that produces it, SPHK1 (sphingosine kinase 1), regulate many processes important for the etiology of cancer. It has been suggested that SPHK1 levels are regulated by the tumor suppressor protein TP53, a key regulator of cell cycle arrest, apoptosis, and macroautophagy/autophagy. However, little is still known of the relationship between TP53 and SPHK1 activity in the regulation of these processes. To explore this link, we examined the effects of inhibiting SPHK1 in wild-type and TP53 null cancer cell lines...
January 25, 2018: Autophagy
Jia Cui, William J Placzek
Anti-apoptotic B cell lymphoma 2 (BCL2) family members (BCL2, MCL1, BCLxL, BCLW, and BFL1) are key players in the regulation of intrinsic apoptosis. Dysregulation of these proteins not only impairs normal development, but also contributes to tumor progression and resistance to various anti-cancer therapies. Therefore, cells maintain strict control over the expression of anti-apoptotic BCL2 family members using multiple mechanisms. Over the past two decades, the importance of post-transcriptional regulation of mRNA in controlling gene expression and its impact on normal homeostasis and disease have begun to be appreciated...
January 20, 2018: International Journal of Molecular Sciences
Federico Lucantoni, Andreas U Lindner, Norma O'Donovan, Heiko Düssmann, Jochen H M Prehn
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis...
January 19, 2018: Cell Death & Disease
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