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https://www.readbyqxmd.com/read/28336294/palmitate-mediated-diacylglycerol-accumulation-causes-endoplasmic-reticulum-stress-plin2-degradation-and-cell-death-in-h9c2-cardiomyoblasts
#1
Ali Akoumi, Taha Haffar, Maria Mousterji, Robert Scott Kiss, Nicolas Bousette
We have previously shown that palmitate causes ER stress in primary cardiomyocytes and this was associated with a diffuse lipid staining histology. In contrast, oleate, which was non-toxic, led to the formation of abundant, clearly delineated lipid droplets. The aberrant lipid histology in palmitate treated cells led us to hypothesize that perhaps there was an impairment in lipid droplet formation, which could lead to accumulation of lipids in the ER and consequent ER stress. To test this hypothesis we treated H9C2s (a cardiomyoblast cell line) with either 300µM oleate or palmitate for 8h...
March 21, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28323983/autophagic-degradation-of-collagen-1a1-by-cortisol-in-human-amnion-fibroblasts
#2
Yabing Mi, Wangsheng Wang, Chuyue Zhang, Chao Liu, Jiangwen Lu, Wenjiao Li, Rujuan Zuo, Leslie Myatt, Kang Sun
Rupture of fetal membranes can initiate parturition at both term and preterm. Collagen is the crucial factor determining the tensile strength of the membranes. Toward the end of gestation, a feed-forward regeneration of cortisol via 11β-hydroxysteroid dehydrogenase 1 exists in fetal membranes. It remains undetermined whether cortisol contributes to collagen reduction in fetal membranes. Here we have examined whether cortisol accumulation is a causative factor for collagen reduction in human amnion fibroblasts, the major source of collagens in the membranes...
January 17, 2017: Endocrinology
https://www.readbyqxmd.com/read/28322449/tgf-%C3%AE-inhibits-osteogenesis-by-upregulating-the-expression-of-ubiquitin-ligase-smurf1-via-mapk-erk-signaling
#3
Xuewu Sun, Ziang Xie, Yan Ma, Xin Pan, Jiying Wang, Zhijun Chen, Peihua Shi
High incidence of osteoporotic fractures emphasizes the necessity of developing effective measures to promote osteogenesis. In our study, we investigated a possible role of MAPK-ERK signaling in the TGF-β-mediated osteoblastic differentiation. Our results indicated that TGF-β activated the MAPK-ERK pathway and inhibited osteogenesis in mesenchymal pluripotent cell line, C3H10T1/2, and preosteoblastic cell line, MC3T3 cells. And the downregulation of MAPK-ERK signaling using pharmacological inhibitor U0126 and RNA interference rescued osteoblast differentiation suppressed by TGF-β, which was confirmed by Alkaline phosphatase (ALP) staining and alizarrn red staining and the enhanced expression of osteogenesic markers...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28315668/cmybp-c-was-decreased-via-klhl3-mediated-proteasomal-degradation-in-congenital-heart-diseases
#4
Leitong Wang, Guangrui Lai, Guoming Chu, Xiaoyan Liang, Yanyan Zhao
Cardiac myosin binding protein C (cMyBP-C) is a cardiac structural and regulatory protein; mutations of cMyBP-C are frequently associated with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Cardiac special transcription factors may regulate the expression of cMyBP-C. However, the role of cMyBP-C in congenital heart diseases (CHD) remains poorly understood. In the current study, western blotting and the MRM approach showed that cMyBP-C expression was significantly reduced in fetuses with CHD compared to those without...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#5
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
https://www.readbyqxmd.com/read/28283022/disruption-of-twist1-rela-binding-by-mutation-and-competitive-inhibition-to-validate-the-twist1-wr-domain-as-a-therapeutic-target
#6
Cai M Roberts, Sophia A Shahin, Joana Loeza, Thanh H Dellinger, John C Williams, Carlotta A Glackin
BACKGROUND: Most cancer deaths result from tumor cells that have metastasized beyond their tissue of origin, or have developed drug resistance. Across many cancer types, patients with advanced stage disease would benefit from a novel therapy preventing or reversing these changes. To this end, we have investigated the unique WR domain of the transcription factor TWIST1, which has been shown to play a role in driving metastasis and drug resistance. METHODS: In this study, we identified evolutionarily well-conserved residues within the TWIST1 WR domain and used alanine substitution to determine their role in WR domain-mediated protein binding...
March 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28278502/kaempferol-modulates-dna-methylation-and-downregulates-dnmt3b-in-bladder-cancer
#7
Wei Qiu, Jun Lin, Yichen Zhu, Jian Zhang, Liping Zeng, Ming Su, Ye Tian
BACKGROUND: Genomic DNA methylation plays an important role in both the occurrence and development of bladder cancer. Kaempferol (Kae), a natural flavonoid that is present in many fruits and vegetables, exhibits potent anti-cancer effects in bladder cancer. Similar to other flavonoids, Kae possesses a flavan nucleus in its structure. This structure was reported to inhibit DNA methylation by suppressing DNA methyltransferases (DNMTs). However, whether Kae can inhibit DNA methylation remains unclear...
March 8, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28235656/high-expressing-cystic-fibrosis-transmembrane-conductance-regulator-interacts-with-histone-deacetylase-2-to-promote-the-development-of-ph-leukemia-through-the-hdac2-mediated-pten-pathway
#8
Tianyou Yan, Yamei Leng, Xi Yang, Yuping Gong, Huaqin Sun, Ke Wang, Wenming Xu, Yuhuan Zheng, Duolan Naren, Rui Shi
The aberrant expression or mutation of CFTR has been shown to be involved in several tumors, but how mutations or dysfunction of CFTR may increase the risk of malignancies in various tissues remains unclear. Here, we report the interaction between CFTR and HDAC2, and its involvement in the development of Ph+ leukemia. We first detected the physical interaction and co-localization of CFTR and HDAC2 in Ph+ leukemia cell lines. And treatment with CFTRinh-172, a CFTR inhibitor, reduced the expression of HDAC2 protein in K562 and SUP-B15 cells, which could be partially recovered by MG132, a proteasome inhibitor...
February 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28220348/proteasome-inhibitor-mg132-induces-thyroid-cancer-cell-apoptosis-by-modulating-the-activity-of-transcription-factor-foxo3a
#9
Wei Qiang, Fang Sui, Jingjing Ma, Xinru Li, Xiaojuan Ren, Yuan Shao, Jiazhe Liu, Haixia Guan, Bingyin Shi, Peng Hou
Proteasome inhibitors are promising antitumor drugs with preferable cytotoxicity in malignant cells and have exhibited clinical efficiency in several hematologic malignancies. P53-dependent apoptosis has been reported to be a major mechanism underlying. However, apoptosis can also be found in cancer cells with mutant-type p53, suggesting the involvement of p53-independent mechanism. Tumor suppressor forkhead Box O3 is another substrate of proteasomal degradation, which also functions partially through inducing apoptosis...
February 20, 2017: Endocrine
https://www.readbyqxmd.com/read/28218462/tungsten-exposure-causes-a-selective-loss-of-histone-demethylase-protein
#10
Freda Laulicht Glick, Feng Wu, Xiaoru Zhang, Ashley Jordan, Jason Brocato, Thomas Kluz, Hong Sun, Max Costa
In the course of our investigations into the toxicity of tungstate, we discovered that cellular exposure resulted in the loss of the histone demethylase protein. We specifically investigated the loss of two histone demethylase dioxygenases, JARID1A and JMJD1A. Both of these proteins were degraded in the presence of tungstate and this resulted in increased global levels of H3K4me3 and H3K9me2, the substrates of JARID1A and JMJD1A respectively. Treatment with MG132 completely inhibited the loss of the demethylase proteins induced by tungstate treatment, suggesting that tungstate activated the proteasomal degradation of these proteins...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28196083/cacybp-sip-promotes-the-proliferation-of-colon-cancer-cells
#11
Huihong Zhai, Yongquan Shi, Xiong Chen, Jun Wang, Yuanyuan Lu, Faming Zhang, Zhengxiong Liu, Ting Lei, Daiming Fan
CacyBP/SIP is a component of the ubiquitin pathway and is overexpressed in several transformed tumor tissues, including colon cancer, which is one of the most common cancers worldwide. It is unknown whether CacyBP/SIP promotes the proliferation of colon cancer cells. This study examined the expression level, subcellular localization, and binding activity of CacyBP/SIP in human colon cancer cells in the presence and absence of the hormone gastrin. We found that CacyBP/SIP was expressed in a high percentage of colon cancer cells, but not in normal colonic surface epithelium...
2017: PloS One
https://www.readbyqxmd.com/read/28186089/adenovirus-mediated-tipe2-overexpression-inhibits-gastric-cancer-metastasis-via-reversal-of-epithelial-mesenchymal-transition
#12
H Yin, X Huang, M Tao, Q Hu, J Qiu, W Chen, J Wu, Y Xie
Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TNFAIP8L2; also termed TIPE2) has been shown to be involved in both the immune-negative modulation and cancer. We previously found that TIPE2 is lost in human gastric cancer, and TIPE2 restoration suppresses gastric cancer growth by induction of apoptosis and impairment of protein kinase B (PKB/AKT) and extracellular signal-regulated kinase-1/2 (ERK1/2) signaling. However, its correlation with epithelial-mesenchymal transition (EMT) in gastric cancer is largely elusive...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28182699/bifunctional-effects-of-o-methylated-flavones-from-scutellaria-baicalensis-georgi-on-melanocytes-inhibition-of-melanin-production-and-intracellular-melanosome-transport
#13
Michiko Kudo, Kumiko Kobayashi-Nakamura, Kentaro Tsuji-Naito
The growing interest in skin lightening has recently renewed attention on the esthetic applications of Chinese herbal medicine. Although Scutellaria baicalensis Georgi is used for antipyretic and antiinflammatory purposes, its whitening effect remains unclear. This study reports three major findings: (1) S. baicalensis has a potent inhibitory effect on melanogenesis; (2) wogonin and its glycoside are the active components of S. baicalensis; and (3) O-methylated flavones from S. baicalensis, such as wogonin, inhibit intracellular melanosome transport...
2017: PloS One
https://www.readbyqxmd.com/read/28152014/apigenin-selective-ck2-inhibitor-increases-ikaros-expression-and-improves-t-cell-homeostasis-and-function-in-murine-pancreatic-cancer
#14
Nadine Nelson, Karoly Szekeres, Cristina Iclozan, Ivannie Ortiz Rivera, Andrew McGill, Gbemisola Johnson, Onyekachi Nwogu, Tomar Ghansah
Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model...
2017: PloS One
https://www.readbyqxmd.com/read/28142215/brief-report-proteasomal-indoleamine-2-3-dioxygenase-degradation-reduces-the-immunosuppressive-potential-of-clinical-grade-mesenchymal-stromal-cells-undergoing-replicative-senescence
#15
Séverine Loisel, Joëlle Dulong, Cédric Ménard, Marie-Laure Renoud, Nadine Meziere, Bezier Isabelle, Maëlle Latour, Nadège Bescher, Rémy Pedeux, Nicolas Bertheuil, Erwan Flecher, Luc Sensebé, Karin Tarte
Owing to their immunosuppressive properties, mesenchymal stromal cells (MSCs) obtained from bone marrow (BM-MSCs) or adipose tissue (ASCs) are considered a promising tool for cell therapy. However, important issues should be considered to ensure the reproducible production of efficient and safe clinical-grade MSCs. In particular, high expansion rate, associated with progressive senescence, was recently proposed as one of the parameters that could alter MSC functionality. In this study, we directly address the consequences of replicative senescence on BM-MSC and ASC immunomodulatory properties...
January 31, 2017: Stem Cells
https://www.readbyqxmd.com/read/28122580/identification-of-small-molecule-modulators-of-hiv-1-tat-and-rev-protein-accumulation
#16
Ahalya Balachandran, Raymond Wong, Peter Stoilov, Sandy Pan, Benjamin Blencowe, Peter Cheung, P Richard Harrigan, Alan Cochrane
BACKGROUND: HIV-1 replication is critically dependent upon controlled processing of its RNA and the activities provided by its encoded regulatory factors Tat and Rev. A screen of small molecule modulators of RNA processing identified several which inhibited virus gene expression, affecting both relative abundance of specific HIV-1 RNAs and the levels of Tat and Rev proteins. RESULTS: The screen for small molecules modulators of HIV-1 gene expression at the post-transcriptional level identified three (a pyrimidin-7-amine, biphenylcarboxamide, and benzohydrazide, designated 791, 833, and 892, respectively) that not only reduce expression of HIV-1 Gag and Env and alter the accumulation of viral RNAs, but also dramatically decrease Tat and Rev levels...
January 26, 2017: Retrovirology
https://www.readbyqxmd.com/read/28117552/oscesa9-conserved-site-mutation-leads-to-largely-enhanced-plant-lodging-resistance-and-biomass-enzymatic-saccharification-by-reducing-cellulose-dp-and-crystallinity-in-rice
#17
Fengcheng Li, Guosheng Xie, Jiangfeng Huang, Ran Zhang, Yu Li, Miaomiao Zhang, Yanting Wang, Ao Li, Xukai Li, Tao Xia, Chengcheng Qu, Fan Hu, Arthur J Ragauskas, Liangcai Peng
Genetic modification of plant cell walls has been posed to reduce lignocellulose recalcitrance for enhancing biomass saccharification. Since cellulose synthase (CESA) gene is first identified, several dozen CESA mutants have been reported, but almost all mutants exhibit the defective phenotypes in plant growth and development. In this study, the rice (Oryza sativa) Osfc16 mutant with substitutions (W481C, P482S) at P-CR conserved-site in CESA9 shows a slightly affected plant growth and higher biomass yield by 25%-41% compared with wild type (Nipponbare, a japonica variety)...
January 24, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28115710/differential-control-of-retrovirus-silencing-in-embryonic-cells-by-proteasomal-regulation-of-the-zfp809-retroviral-repressor
#18
Cheng Wang, Stephen P Goff
Replication of the murine leukemia viruses is strongly suppressed in mouse embryonic stem (ES) cells. Proviral DNAs are formed normally but are then silenced by a large complex bound to DNA by the ES cell-specific zinc-finger protein ZFP809. We show here that ZFP809 expression is not regulated by transcription but rather by protein turnover: ZFP809 protein is stable in embryonic cells but highly unstable in differentiated cells. The protein is heavily modified by the accumulation of polyubiquitin chains in differentiated cells and stabilized by the proteasome inhibitor MG132...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28114332/a-novel-single-nucleotide-t980c-polymorphism-in-the-human-carboxypeptidase-e-gene-results-in-loss-of-neuroprotective-function
#19
Lin Cong, Yong Cheng, Niamh X Cawley, Saravana R K Murthy, Y Peng Loh
Report of a human with a homozygous truncating null mutation of the Carboxypeptidase E (CPE) gene with endocrinological and neurological deficits prompted us to search for other mutations in the human CPE gene that might be linked to disease. We searched an EST database and identified from a small population of patients, a novel T to C single nucleotide polymorphism (SNP) in the CPE gene at bp980 of exon 4, herein called TC-CPE. This introduces a tryptophan to arginine (W235R) mutation in the catalytic domain of human CPE protein...
2017: PloS One
https://www.readbyqxmd.com/read/28106491/effect-of-an-mg132-sustained-drug-delivery-capsular-ring-on-the-inhibition-of-posterior-capsule-opacification-in-a-rabbit-model
#20
Xuan Bao, Min Hou, Yingyan Qin, Furong Luo, Fu Shang, Mingxing Wu
PURPOSE: To design an MG132-sustained drug delivery capsular ring (SDDCR) and investigate its effect on the inhibition of posterior capsule opacification (PCO) in a rabbit model. METHODS: The SDDCRs were prepared by forming a slice of film made by the mixture of poly lactic-co-glycolic acid (PLGA) and MG132 on the surface of capsular tension rings (CTRs). The drug-loading capacity, entrapment efficiency, and in vitro release of the drug-containing film were detected...
March 2017: Journal of Ocular Pharmacology and Therapeutics
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