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https://www.readbyqxmd.com/read/29299204/downregulation-of-microrna-125a-is-involved-in-intervertebral-disc-degeneration-by-targeting-pro-apoptotic-bcl-2-antagonist-killer-1
#1
Ping Liu, Feng Chang, Ting Zhang, Gang Gao, Chen Yu, Sheng-Qiang Ding, Gen-Le Zuo, Xin-Hu Huang
Objectives: To investigate the role of the microRNA-125a (miR-125a) and BAK1 in intervertebral disc degeneration (IDD). Materials and Methods: Degenerative lumbar nucleus pulposus (NP) tissues were obtained from 193 patients who underwent resection, and normal controls consisted of normal NP tissues from 32 patients with traumatic lumbar fracture in our hospital. All patients were graded according to the Pfirrmann criteria. QRT-PCR was used to detect the expression of miR-125a and BAK1, and apoptosis of NP tissues detected by TUNEL staining...
November 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29296753/an-aptamer-based-targeted-delivery-of-mir-26a-protects-mice-against-chemotherapy-toxicity-while-suppressing-tumor-growth
#2
Toshihiko Tanno, Peng Zhang, Christopher A Lazarski, Yang Liu, Pan Zheng
The efficacy of traditional chemotherapy is limited by its toxicity, especially with regard to hematopoiesis. Here we show that miR-26a plays a critical role in protecting mice against chemotherapy-induced myeloid suppression by targeting a proapoptotic protein (Bak1) in hematopoietic stem/progenitor cells (HSPCs). Because c-Kit is expressed at high levels in HSPCs, we designed a microRNA-aptamer chimera that contains miR-26a mimic and c-Kit-targeting aptamer and successfully delivered miR-26a into HSPCs to attenuate toxicity of 5' fluorouracil (5-FU) and carboplatin...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288738/vacuole-integrity-maintained-by-duf300-proteins-is-required-for-brassinosteroid-signaling-regulation
#3
Qinsong Liu, Thomas Vain, Corrado Viotti, Siamsa M Doyle, Danuše Tarkowská, Ondřej Novák, Cyril Zipfel, Folke Sitbon, Stéphanie Robert, Daniel Hofius
Brassinosteroid (BR) hormone signaling controls multiple processes during plant growth and development and is initiated at the plasma membrane through the receptor kinase BRASSINOSTEROID INSENSITIVE1 (BRI1) together with co-receptors such as BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1). BRI1 abundance is regulated by endosomal recycling and vacuolar targeting, but the role of vacuole-related proteins in BR receptor dynamics and BR responses remain elusive. Here, we show that the absence of two DUF300 domain-containing tonoplast proteins, LAZARUS1 (LAZ1) and LAZ1 HOMOLOG1 (LAZ1H1), causes vacuole morphology defects, growth inhibition, and constitutive activation of BR signaling...
December 27, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29234488/sirt6-histone-deacetylase-functions-as-a-potential-oncogene-in-human-melanoma
#4
Liz Mariely Garcia-Peterson, Mary Ann Ndiaye, Chandra K Singh, Gagan Chhabra, Wei Huang, Nihal Ahmad
Melanoma is an aggressive skin cancer that can rapidly metastasize to become fatal, if not diagnosed early. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, novel molecular targets and strategies are required to manage this neoplasm. This study was undertaken to determine the role of the sirtuin SIRT6 in melanoma. Employing a panel of human melanoma cells and normal human melanocytes, we found significant SIRT6 mRNA and protein upregulation in melanoma cells. Further, using a tissue microarray coupled with quantitative Vectra analysis, we demonstrated significant SIRT6 overexpression in human melanoma tissues...
September 2017: Genes & Cancer
https://www.readbyqxmd.com/read/29231977/dids-inhibits-overexpression-bak1-induced-mitochondrial-apoptosis-through-gsk3%C3%AE-%C3%AE-catenin-signaling-pathway
#5
Xiayun Yang, Shusheng Tang, Daowen Li, Xiaohong Yu, Fuyun Wang, Xilong Xiao
Bcl-2 homologous antagonist/killer (BAK1) is a critical regulator of mitochondrial apoptosis. Although upregulation of BAK1 induces apoptosis has been established, the underlying molecular mechanism is far from clear. 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), an organic anion used as a blocker of anion exchangers and chloride channels, has been proved to rescue cell apoptosis both in vitro and in vivo. However, whether DIDS can inhibit BAK1-induced mitochondrial apoptosis remains undefined. Thus, this study aimed to explore whether DIDS could protect BAK1-induced apoptosis through GSK3β/β-catenin signaling pathway...
December 12, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29211989/allosteric-control-of-a-plant-receptor-kinase-through-s-glutathionylation
#6
Alexander S Moffett, Kyle W Bender, Steven C Huber, Diwakar Shukla
Growing evidence supports the importance of protein S-glutathionylation as a regulatory post-translational modification with functional consequences for proteins. Discoveries of redox-state-dependent protein kinase S-glutathionylation have fueled discussion of redox-sensitive signaling. Following previously published experimental evidence for S-glutathionylation induced deactivation of the Arabidopsis thaliana kinase BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED RECEPTOR-LIKE KINASE 1 (BAK1), we investigated the consequences of S-glutathionylation on the equilibrium conformational ensemble of BAK1 using all-atom molecular dynamics simulations...
December 5, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29194674/a-whole-genome-sequence-association-study-for-puberty-in-a-large-duroc%C3%A2-%C3%A3-%C3%A2-erhualian-f2-population
#7
W S Xin, F Zhang, G R Yan, W W Xu, S J Xiao, Z Y Zhang, L S Huang
A large proportion of gilts and sows are culled from reproduction populations because of anestrus and pubertal reproductive failure. Selecting early onset of puberty gilts has a favorable effect on sows' reproductivity. However, age at puberty is hard to be routinely measured in commercial herds. With molecular genetic predictors, identifying individuals that have a propensity for early onset of puberty can be simplified. We previously performed genome scanning and a genome-wide association study for puberty in an F2 resource population using 183 microsatellites and 62 125 SNPs respectively...
December 1, 2017: Animal Genetics
https://www.readbyqxmd.com/read/29150546/differential-regulation-of-two-tiered-plant-immunity-and-sexual-reproduction-by-anxur-receptor-like-kinases
#8
Hyunggon Mang, Baomin Feng, Zhangjian Hu, Aurélien Boisson-Dernier, Christina M Franck, Xiangzong Meng, Yanyan Huang, Jinggeng Zhou, Guangyuan Xu, Taotao Wang, Libo Shan, Ping He
Plants have evolved two tiers of immune receptors to detect infections: cell surface-resident pattern recognition receptors (PRRs) that sense microbial signatures and intracellular nucleotide binding domain leucine-rich repeat (NLR) proteins that recognize pathogen effectors. How PRRs and NLRs interconnect and activate the specific and overlapping plant immune responses remains elusive. A genetic screen for components controlling plant immunity identified ANXUR1 (ANX1), a malectin-like domain-containing receptor-like kinase, together with its homolog ANX2, as important negative regulators of both PRR- and NLR-mediated immunity in Arabidopsis thaliana ANX1 constitutively associates with the bacterial flagellin receptor FLAGELLIN-SENSING2 (FLS2) and its coreceptor BRI1-ASSOCIATED RECEPTOR KINASE1 (BAK1)...
December 2017: Plant Cell
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
#9
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/29148970/autophagic-cell-death-is-dependent-on-lysosomal-membrane-permeability-through-bax-and-bak
#10
Jason Karch, Tobias G Schips, Bryan D Maliken, Matthew J Brody, Michelle A Sargent, Onur Kanisciak, Jeffery D Molkentin
Cells deficient in the pro-death Bcl-2 family members Bax and Bak are known to be resistant to apoptotic cell death, and previous we have shown that these two effectors are also needed for mitochondrial-dependent cellular necrosis (Karch et al., 2013). Here we show that mouse embryonic fibroblasts deficient in Bax/Bak1 are resistant to the third major form of cell death associated with autophagy through a mechanism involving lysosome permeability. Indeed, specifically targeting Bax only to the lysosome restores autophagic cell death in Bax/Bak1 null cells...
November 17, 2017: ELife
https://www.readbyqxmd.com/read/29144987/benzo-a-pyren-7-8-dihydrodiol-9-10-epoxide-induces-human-trophoblast-swan-71-cell-dysfunctions-due-to-cell-apoptosis-through-disorder-of-mitochondrial-fission-fusion
#11
Weiping Wang, Rong Wang, Qiao Zhang, Gil Mor, Huidong Zhang
Benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE) is an endocrine disrupter and ultimate carcinogenic product of benzo(a)pyrene (BaP). Numerous studies have shown that BPDE causes trophoblast-related diseases, such as preeclampsia, growth restriction or miscarriages. However, the underlying mechanism, especially the mitochondria-related BPDE-induced trophoblast dysfunction remains unknown. In this study, we examined mitochondrial functions in BPDE-induced human trophoblast cell line Swan 71. BPDE decreased cell ability, attenuated cell invasion and HCG secretion, induced cell apoptosis, decreased mitochondrial membrane potential, increased reactive oxygen species (ROS) and MDA, and decreased SOD activity in a dose-dependent manner...
November 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29122578/a-carvedilol-responsive-microrna-mir-125b-5p-protects-the-heart-from-acute-myocardial-infarction-by-repressing-pro-apoptotic-bak1-and-klf13-in-cardiomyocytes
#12
Ahmed S Bayoumi, Kyoung-Mi Park, Yongchao Wang, Jian-Peng Teoh, Tatsuya Aonuma, Yaoliang Tang, Huabo Su, Neal L Weintraub, Il-Man Kim
BACKGROUND: Cardiac injury is accompanied by dynamic changes in the expression of microRNAs (miRs), small non-coding RNAs that post-transcriptionally regulate target genes. MiR-125b-5p is downregulated in patients with end-stage dilated and ischemic cardiomyopathy, and has been proposed as a biomarker of heart failure. We previously reported that the β-blocker carvedilol promotes cardioprotection via β-arrestin-biased agonism of β1-adrenergic receptor while stimulating miR-125b-5p processing in the mouse heart...
November 7, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29099481/viewing-bcl2-and-cell-death-control-from-an-evolutionary-perspective
#13
REVIEW
Andreas Strasser, David L Vaux
The last 30 years of studying BCL2 have brought cell death research into the molecular era, and revealed its relevance to human pathophysiology. Most, if not all metazoans use an evolutionarily conserved process for cellular self destruction that is controlled and implemented by proteins related to BCL2. We propose the anti-apoptotic BCL2-like and pro-apoptotic BH3-only members of the family arose through duplication and modification of genes for the pro-apoptotic multi-BH domain family members, such as BAX and BAK1...
November 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29083116/non-branched-%C3%AE-1-3-glucan-oligosaccharides-trigger-immune-responses-in-arabidopsis
#14
Hugo Mélida, Sara Sopeña-Torres, Laura Bacete, María Garrido-Arandia, Lucía Jordá, Gemma López, Antonio Muñoz, Luis F Pacios, Antonio Molina
Fungal cell walls, essential for environmental adaptation and host colonization, have been evolutionarily selected by plants and animals as a source of Microbe-Associated Molecular Patterns (MAMPs) that upon recognition by host Pattern Recognition Receptors (PRRs) trigger immune responses conferring disease resistance. Chito-oligosaccharides (β-1,4-N-acetylglucosamine oligomers, (GlcNAc)n ) are the only glycosidic structures from fungal walls well-shown to function as MAMPs in plants. Perception of (GlcNAc)4-8 by Arabidopsis involves CERK1, LYK4 and LYK5, three of the eight members of LysM PRR family...
October 30, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/29068240/a-verticillium-dahliae-extracellular-cutinase-modulates-plant-immune-responses
#15
Yuejing Gui, Wenqi Zhang, Dandan Zhang, Lei Zhou, Dylan P G Short, Jie Wang, Xuefeng Ma, Tinggang Li, Zhiqiang Kong, Bao-Li Wang, Dan Wang, Nanyang Li, Krishna Subbarao, Jie-Yin Chen, Xiaofeng Dai
Cutinases have been implicated as important enzymes during the process of fungal infection of aerial plant organs. The function of cutinases in the disease cycle of fungal pathogens that invade plants through the roots has been less studied. Here, functional analysis of thirteen cutinase (carbohydrate esterase family 5 domain-containing) genes (VdCUTs) in the highly virulent vascular wilt pathogen Verticillium dahliae Vd991 was performed. Significant sequence divergence in cutinase family members was observed in the genome of V...
October 25, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29066854/2snp-heritability-and-effects-of-genetic-variants-for-neutrophil-to-lymphocyte-and-platelet-to-lymphocyte-ratio
#16
Bochao Danae Lin, Elena Carnero-Montoro, Jordana T Bell, Dorret I Boomsma, Eco J de Geus, Rick Jansen, Cornelis Kluft, Massimo Mangino, Brenda Penninx, Tim D Spector, Gonneke Willemsen, Jouke-Jan Hottenga
Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are important biomarkers for disease development and progression. To gain insight into the genetic causes of variance in NLR and PLR in the general population, we conducted genome-wide association (GWA) analyses and estimated SNP heritability in a sample of 5901 related healthy Dutch individuals. GWA analyses identified a new genome-wide significant locus on the HBS1L-MYB intergenic region for PLR, which replicated in a sample of 2538 British twins...
November 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/29062863/the-vacuolar-h-atpase-v0-subunit-d2-is-associated-with-chondrocyte-hypertrophy-and-supports-chondrocyte-differentiation
#17
Babatunde A Ayodele, Michiko Mirams, Charles N Pagel, Eleanor J Mackie
Chondrocyte hypertrophy makes important contributions to bone development and growth. We have investigated a number of novel cartilage genes identified in a recent transcriptomic study to determine whether they are differentially expressed between different zones of equine foetal growth cartilage. Twelve genes (ATP6V0D2, BAK1, DDX5, GNB1, PIP4K2A, RAP1B, RPS7, SRSF3, SUB1, TMSB4, TPI1 and WSB2) were found to be more highly expressed in the zone of hypertrophic chondrocytes than in the reserve or proliferative zones, whereas FOXA3 and SERPINA1 were expressed at lower levels in the hypertrophic zone than in the reserve zone...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/29048629/inhibition-of-neuroblastoma-proliferation-by-pf-3758309-a-small-molecule-inhibitor-that-targets-p21-activated-kinase-4
#18
Zhiheng Li, Xiaolu Li, Lixiao Xu, Yanfang Tao, Chun Yang, Xiaolan Chen, Fang Fang, Yi Wu, Xin Ding, He Zhao, Mei Li, Guanghui Qian, Yunyun Xu, Junli Ren, Weiwei Du, Jian Wang, Jun Lu, Shaoyan Hu, Jian Pan
Neuroblastoma is the most common extracranial solid childhood tumor. Despite the availability of advanced multimodal therapy, high-risk patients still have low survival rates. p21-activated kinase 4 (PAK4) has been shown to regulate many cellular processes in cancer cells, including migration, polarization and proliferation. However, the role of PAK4 in neuroblastoma remains unclear. In the present study, we demonstrated that PAK4 was overexpressed in neuroblastoma tissues and was correlated with tumor malignance and prognosis...
September 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29028796/bak1-is-involved-in-atralf1-induced-inhibition-of-root-cell-expansion
#19
Keini Dressano, Paulo H O Ceciliato, Aparecida L Silva, Juan Carlos Guerrero-Abad, Tábata Bergonci, Fausto Andrés Ortiz-Morea, Marco Bürger, Marcio C Silva-Filho, Daniel S Moura
The rapid alkalinization factor (RALF) peptide negatively regulates cell expansion, and an antagonistic relationship has been demonstrated between AtRALF1, a root-specific RALF isoform in Arabidopsis, and brassinosteroids (BRs). An evaluation of the response of BR signaling mutants to AtRALF1 revealed that BRI1-associated receptor kinase1 (bak1) mutants are insensitive to AtRALF1 root growth inhibition activity. BAK1 was essential for the induction of AtRALF1-responsive genes but showed no effect on the mobilization of Ca2+ and alkalinization responses...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29023762/tolerance-of-olive-olea-europaea-cv-frantoio-to-verticillium-dahliae-relies-on-both-basal-and-pathogen-induced-differential-transcriptomic-responses
#20
María de la O Leyva-Pérez, Jaime Jiménez-Ruiz, Carmen Gómez-Lama Cabanás, Antonio Valverde-Corredor, Juan B Barroso, Francisco Luque, Jesús Mercado-Blanco
Verticillium wilt of olive (VWO) is one of the most serious biotic constraints for this tree crop. Our knowledge of the genetics of the tolerance/resistance to this disease is very limited. Here we show that tolerance of the cv Frantoio relies on both basal and early pathogen-induced differential transcriptomic responses. A comparative transcriptomic analysis (RNA-seq) was conducted in root tissues of cvs Frantoio (VWO-tolerant) and Picual (VWO-susceptible). RNA samples originated from roots of inoculated olive plants during the early infection stages by Verticillium dahliae (highly virulent, defoliating pathotype)...
October 12, 2017: New Phytologist
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