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排序方式: 共有104条查询结果,搜索用时 15 毫秒
61.
Manman Wang Hao Guo Xuechun Zhang Xiyang Wang Hu Tao Tan Zhang Min Peng Min Zhang Zan Huang 《Translational oncology》2022,15(1)
Clinic therapy of acute myeloid leukemia (AML) remains unsatisfactory that urges for development of novel strategies. Recent studies identified ANP32A as a novel biomarker of unfavorable outcome of leukemia, which promoted leukemogenesis by increasing H3 acetylation and the expression of lipid metabolism genes. It is of great significance to investigate whether targeting ANP32A is a novel strategy for leukemia therapy. To target ANP32A, we identified a peptide that competed with ANP32A to bind to histone 3 (termed as H3-binding peptide, H3BP). Disrupting ANP32A and H3 interaction by the overexpression of H3BP-GFP fusion protein mimicked the effect of ANP32A knockdown, impaired H3 acetylation on multiple locus of target genes, reduced proliferation, and caused apoptosis in leukemia cells. Furthermore, a synthesized membrane-penetrating peptide TAT-H3BP effectively entered into leukemia cells and phenocopied such effect. In vivo, TAT-H3BP showed potent efficacy against leukemia: Intra-tumor injection of TAT-H3BP significantly reduced the volume of subcutaneous tumors in nude mice and recipient mice engrafted with TAT-H3BP-pretreated 6133/MPL W515L cells exhibited ameliorated leukemia burden and prolonged survival. Noticeably, TAT-H3BP efficiently suppressed proliferation and colony-forming unit of human primary AML cells without affecting normal cord blood cells. Our findings demonstrate that intervening the physical interaction of ANP32A with H3 impairs the oncogenicity of ANP32A and may be a promising therapeutic strategy against AML. 相似文献
62.
Christine J. Pol Nina M. Pollak Michael J. Jurczak Effimia Zacharia Iordanes Karagiannides Ioannis D. Kyriazis Panagiotis Ntziachristos Diego A. Scerbo Brett R. Brown Iannis Aifantis Gerald I. Shulman Ira J. Goldberg Konstantinos Drosatos 《生物化学与生物物理学报:疾病的分子基础》2019,1865(9):2125-2137
Cardiac metabolism affects systemic energetic balance. Previously, we showed that Krüppel-like factor (KLF)-5 regulates cardiomyocyte PPARα and fatty acid oxidation-related gene expression in diabetes. We surprisingly found that cardiomyocyte-specific KLF5 knockout mice (αMHC-KLF5?/?) have accelerated diet-induced obesity, associated with increased white adipose tissue (WAT). Alterations in cardiac expression of the mediator complex subunit 13 (Med13) modulates obesity. αMHC-KLF5?/? mice had reduced cardiac Med13 expression likely because KLF5 upregulates Med13 expression in cardiomyocytes. We then investigated potential mechanisms that mediate cross-talk between cardiomyocytes and WAT. High fat diet-fed αMHC-KLF5?/? mice had increased levels of cardiac and plasma FGF21, while food intake, activity, plasma leptin, and natriuretic peptides expression were unchanged. Consistent with studies reporting that FGF21 signaling in WAT decreases sumoylation-driven PPARγ inactivation, αMHC-KLF5?/? mice had less SUMO-PPARγ in WAT. Increased diet-induced obesity found in αMHC-KLF5?/? mice was absent in αMHC-[KLF5?/?;FGF21?/?] double knockout mice, as well as in αMHC-FGF21?/? mice that we generated. Thus, cardiomyocyte-derived FGF21 is a component of pro-adipogenic crosstalk between heart and WAT. 相似文献
63.
Jianhao Peng Jingjing Jiang Wei Wang Xiaofei Qi Xue-Long Sun Qingyu Wu 《Biochemical and biophysical research communications》2011,411(3):593
B-type natriuretic peptide (BNP) and its related peptides are biomarkers for the diagnosis of heart failure. Recent studies identified several O-glycosylation sites, including Thr-71, on human pro-BNP but the functional significance was unclear. In this study, we analyzed glycosylation and proteolytic processing of pro-BNP in cardiomyocytes. Human pro-BNP wild-type (WT) and mutants were expressed in HEK 293 cells and murine HL-1 cardiomyocytes. Pro-BNP and BNP were analyzed by immunoprecipitation and Western blotting. Glycosidases and glycosylation inhibitors were used to examine carbohydrates on pro-BNP. The effects of furin and corin expression on pro-BNP processing in cells also were examined. We found that in HEK 293 cells, recombinant pro-BNP contained significant amounts of O-glycans with terminal oligosialic acids. Mutation at Thr-71 reduced O-glycans on pro-BNP and increased pro-BNP processing. In HL-1 cardiomyocytes, residue Thr-71 contained little O-glycans, and pro-BNP WT and T71A mutant were processed similarly. In HEK 293 cells, pro-BNP was processed by furin. Mutations at Arg-73 and Arg-76, but not Lys-79, prevented pro-BNP processing. In HL-1 cardiomyocytes, which express furin and corin, single or double mutations at Arg-73, Arg-76 and Lys-79 did not prevent pro-BNP processing. Only when all these three residues were mutated, was pro-BNP processing completely blocked. Our data indicate that pro-BNP glycosylation in cardiomyocytes differed significantly from that in HEK 293 cells. In HEK 293 cells, furin cleaved pro-BNP at Arg-76 whereas in cardiomyocytes corin cleaved pro-BNP at multiple residues including Arg-73, Arg-76 and Lys-79. 相似文献
64.
Qiu-li Zhang Bai-ri Cui Hai-yan Li Ping Li Lan Hong Li-ping Liu Da-zhi Ding Xun Cui 《Biochemical and biophysical research communications》2013
Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways are pivotal and intensively studied signaling pathways in hypoxic conditions. However, the roles of MAPK and PI3K in the regulation of hypoxia-induced atrial natriuretic peptide (ANP) secretion are not well understood. The purpose of the present study was to investigate the mechanism by which the MAPK/ERK (extracellular signal-regulated kinase) and PI3K signaling pathways regulate the acute hypoxia-induced ANP secretion in isolated beating rabbit atria. An acute hypoxic perfused beating rabbit atrial model was used. The ANP levels in the atrial perfusates were measured by radioimmunoassay, and the hypoxia-inducible factor-1α (HIF-1α) mRNA and protein levels in the atrial tissue were determined by RT-PCR and Western blot. Acute hypoxia significantly increased ANP secretion and HIF-1α mRNA and protein levels. Hypoxia-induced ANP secretion was markedly attenuated by the HIF-1α inhibitors, rotenone (0.5 μmol/L) and CAY10585 (10 μmol/L), concomitantly with downregulation of the hypoxia-induced HIF-1α mRNA and protein levels. PD098059 (30 μmol/L) and LY294002 (30 μmol/L), inhibitors of MAPK and PI3K, markedly abolished the hypoxia-induced ANP secretion and atrial HIF-1α mRNA and protein levels. The hypoxia-suppressed atrial dynamics were significantly attenuated by PD098059 and LY294002. Acute hypoxia in isolated perfused beating rabbit atria, markedly increased ANP secretion through HIF-1α upregulation, which was regulated by the MAPK/ERK and PI3K pathways. ANP appears to be part of the protective program regulated by HIF-1α in the response to acute hypoxic conditions. 相似文献
65.
Nikolaos N. Louros Vassiliki A. Iconomidou Paraskevi L. Tsiolaki Evangelia D. Chrysina Georgios E. Baltatzis Efstratios S. Patsouris Stavros J. Hamodrakas 《FEBS letters》2014
Isolated atrial amyloidosis (IAA) is a common localized form of amyloid deposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of its precursor form (NT-proANP). An ‘aggregation-prone’ heptapeptide (114KLRALLT120) was located within the NT-proANP sequence. This peptide self-assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this ‘aggregation-prone’ segment of NT-proANP may assist in prevention/treatment of IAA, congestive heart failure (CHF) or atrial fibrillation (AF). 相似文献
66.
G Morel P Mesguich J G Chabot M Belles-Isles L Jeandel S Heisler 《Biology of the cell / under the auspices of the European Cell Biology Organization》1989,65(2):181-188
Internalization of 125I-labelled atrial natriuretic peptide ([ 125I]ANP) by rat adrenal glomerulosa cells in vivo was investigated by means of an ultrastructural autoradiographic approach. One to 30 min after IV injection of [125I]ANP, silver grains were found, at the light microscope level, over all glomerulosa cells; coinjection of 20 micrograms of unlabelled ANP inhibited this binding by 64%. At the electron microscope level, the time-course study indicated maximal silver grain densities in plasma membranes 1 min after IV injection; grains were detected in mitochondria (external membranes and matrix) 2 min after injection, with maximal labelling at 15 min. The cytoplasmic matrix was labelled only 30 min after injection. During the time-course, labelling of nuclei, Golgi apparatus, and lysosomes was minimal. The data suggest that after binding to plasma membranes ANP is rapidly internalized and distributed within glomerulosa cells. The association of radioactivity with mitochondria suggests that ANP may have intracellular sites of action complementary to those on plasma membranes. 相似文献
67.
68.
Siqueira R Campos C Colombo R Becker CU Fernandes TR Araújo AS Belló-Klein A 《Cell biochemistry and function》2011,29(7):543-548
Pulmonary arterial hypertension (PAH) is a disease that increases the pulmonary vascular resistance, causing hypertrophy and subsequent right heart failure. Oxidative stress is involved in the pathogenesis of PAH, and estrogen is considered an antioxidant. Thus, the aim of this study was to test the hypothesis that estrogen could attenuate PAH by modulating oxidative stress. Female Wistar rats were ovariectomized or suffered the surgery simulation (sham). After 7 days, subcutaneous pellets with 17β‐estradiol or sunflower oil were implanted. At this time, PAH was induced by means of a single dose of monocrotaline (MCT) (60 mg·kg‐1 i.p.). The experimental groups were as follows: (1) sham, (2) sham + MCT, (3) ovariectomy (O), (4) ovariectomy + MCT (OM), (5) ovariectomy + estrogen replacement + MCT (ORM). Hemodynamic measurements were performed 21 days after MCT or saline. Nonovariectomized animals were assessed in the stage of diestrus. Afterwards, the rats were killed to collect the heart, the lung and the liver to evaluate morphometry. Samples of the right ventricle were used to analyse the reduced glutathione : oxidized glutathione ratio. Lung congestion in the OM group, which was decreased in the ORM group, was observed. Right ventricle end‐diastolic pressure was increased in the OM and the ORM groups. The glutathione ratio decreased in the groups O, OM and ORM. The data suggest that estrogen can exert great influence on the cellular redox balance. The maintenance of physiological estrogen levels may help to avoid the appearance of pulmonary oedema, characteristic of this model of PAH, and right ventricular failure. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
69.
Yinqing Huang Dengyin Wu Xin Zhang Minghua Jiang Chaohui Hu Jiangfeng Lin Jifei Tang Lianpin Wu 《Gene》2014
Tumor necrosis factor superfamily ligands provoke a dilated cardiac phenotype signal through a common scaffolding protein termed tumor necrosis factor receptor-associated factor 2 (Traf2); however, Traf2 signaling in the adult mammalian cardiac hypertrophy is not fully understood. This study was aimed to identify the effect of Traf2 on cardiac hypertrophy and the underlying mechanisms. A significant up-regulation of Traf2 expression was observed in mice failing hearts. To further investigate the role of Traf2 in cardiac hypertrophy, we used cultured neonatal rat cardiomyocytes with gain and loss of Traf2 function and cardiac-specific Traf2-overexpressing transgenic (TG) mice. In cultured cardiomyocytes, Traf2 positively regulated angiotensin II (Ang II)-mediated hypertrophic growth, as detected by [3H]-Leucine incorporation, cardiac myocyte area, and hypertrophic marker protein levels. Cardiac hypertrophy in vivo was produced by constriction of transverse aortic (TAC) in TG mice and their wild-type controls. The extent of cardiac hypertrophy was evaluated by echocardiography as well as by pathological and molecular analyses of heart samples. Traf2 overexpression in the heart remarkably enhanced cardiac hypertrophy, left ventricular dysfunction in mice in response to TAC. Further analysis of the signaling pathway in vitro and in vivo suggested that these adverse effects of Traf2 were associated with the activation of AKT/glycogen synthase kinase 3β (GSK3β). The present study demonstrates that Traf2 serves as a novel mediator that enhanced cardiac hypertrophy by activating AKT/GSK3β signaling. 相似文献
70.
Guanyi Bai Shan Gao Amin Shah Kuichang Yuan Woo Hyun Park Suhn Hee Kim 《Peptides》2009,30(9):1720-1728
Cyclooxygenase (COX) is a key enzyme regulating the production of various prostaglandins (PGs) from arachidonic acid. Angiotensin II has been reported to be an important inflammatory mediator, which increases COX-2. The aim of this study was to determine the role of various PGs and COX-2 in the regulation of atrial natriuretic peptide (ANP) secretion. PGF2α and PGD2 caused dose-dependent increases in ANP release and intra-atrial pressure. The potency for the stimulation of ANP secretion by PGF2α was higher than that by PGD2. In contrast, PGE2, PGI2, PGJ2, and thromboxane A2 did not show any significant effects. The increases in intra-atrial pressure and ANP secretion induced by PGF2α and PGD2 were significantly attenuated by the pretreatment with an inhibitor of PGF2α receptor. By the pretreatment with an inhibitor for phospholipase C (PLC), inositol 3-phosphate (IP3) receptor, protein kinase C (PKC), or myosin light chain kinase (MLCK), PGF2α-mediated increase in ANP secretion and positive inotropy were attenuated. Inhibitor for COX-1 or COX-2 did not cause any significant effects on atrial parameters. In hypertrophied rat atria, PGF2α-induced positive inotropy and ANP secretion were markedly attenuated whereas COX-2 inhibitor stimulated ANP secretion. The expression of COX-2 increased and the expression of PGF2α receptor mRNA decreased in hypertrophied rat atria. These results suggest that PGF2α increased the ANP secretion and positive inotropy through PLC–IP3–PKC–MLCK pathway, and the modulation of ANP secretion by COX-2 inhibitor and PGF2α may partly relate to the development of renal hypertension. 相似文献