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1.
J Environ Pathol Toxicol Oncol ; 40(3): 87-94, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34587407

RESUMO

Annexin A9 (ANXA9) represents an important calcium-dependent phospholipid-binding protein family member and contains a calcium-binding site that is necessary for extracellular matrix proteins. ANXA9 has a significant role in human cancers. However, there is no correlation study existing on ANXA9 in gastric cancer (GC). ANXA9 messenger RNA (mRNA) expression within patients with GC were detected with reverse transcription polymerase chain reaction and its protein expression in GC and GES-1 cells were detected through Western blotting. ANXA9 levels within normal and GC tissue samples were measured by Kaplan-Meier analysis and Oncomine. Transwell migration, colony formation, and cell cycle assay monitored the effects of ANXA9 on cell proliferation and metastasis and growth. Additionally, proteins related to epithelial-mesenchymal transition (EMT) were detected to evaluate the function of ANXA9 within GC cells. Relative to GES-1 cells, ANXA9 expression increased within GC cells. Also, ANXA9 expression increased in GC tissues and indicated an unfavorable prognosis. Furthermore, ANXA9 over-expression within HGC-27 cells increased migrated cells quantity and formed larger and more numerous cell clones; the G1 phase decreased while S and G2 phases increased; whereas ANXA9 knockdown suppressed MGC-803 cell growth and migration. Thus, ANXA9 may influence cell growth, migration and EMT through transforming growth factor ß (TGF-ß) signal transduction pathway. Immunofluorescence analyzed SMAD2/3 and p-SMAD2/3 distribution and expression when ANXA9 was overexpressed in HGC-27 cells. These results predicted that ANXA9 mediated cell migration and growth through TGF-ß signal transduction pathway within GC.


Assuntos
Anexinas/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Fator de Crescimento Transformador beta/metabolismo , Anexinas/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal , Humanos , Transdução de Sinais , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Neoplasias Gástricas/mortalidade , Ensaio Tumoral de Célula-Tronco
2.
Int J Mol Sci ; 22(16)2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34445369

RESUMO

Annexin (Ann) is a polygenic, evolutionarily conserved, calcium-dependent and phospholipid-binding protein family, which plays key roles in plant growth, development, and stress response. However, a comprehensive understanding of CaAnn genes of pepper (Capsicum annuum) at the genome-wide level is limited. Based on the available pepper genomic information, we identified 15 members of the CaAnn gene family. Phylogenetic analysis showed that CaAnn proteins could be categorized into four different orthologous groups. Real time quantitative RT-PCR analysis showed that the CaAnn genes were tissue-specific and were widely expressed in pepper leaves after treatments with cold, salt, and drought, as well as exogenously applied MeJA and ABA. In addition, the function of CaAnn9 was further explored using the virus-induced gene silencing (VIGS) technique. CaAnn9-silenced pepper seedlings were more sensitive to salt stress, reflected by the degradation of chlorophyll, the accumulation of reactive oxygen species (ROS), and the decrease of antioxidant defense capacity. This study provides important information for further study of the role of pepper CaAnn genes and their coding proteins in growth, development, and environmental responses.


Assuntos
Anexinas/genética , Capsicum/crescimento & desenvolvimento , Perfilação da Expressão Gênica/métodos , Tolerância ao Sal , Ácido Abscísico/farmacologia , Acetatos/farmacologia , Capsicum/efeitos dos fármacos , Capsicum/genética , Ciclopentanos/farmacologia , Evolução Molecular , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Especificidade de Órgãos , Oxilipinas/farmacologia , Filogenia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/genética , Sequenciamento Completo do Genoma
3.
Int J Mol Sci ; 22(10)2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34067866

RESUMO

Muscular dystrophies constitute a group of genetic disorders that cause weakness and progressive loss of skeletal muscle mass. Among them, Miyoshi muscular dystrophy 1 (MMD1), limb girdle muscular dystrophy type R2 (LGMDR2/2B), and LGMDR12 (2L) are characterized by mutation in gene encoding key membrane-repair protein, which leads to severe dysfunctions in sarcolemma repair. Cell membrane disruption is a physiological event induced by mechanical stress, such as muscle contraction and stretching. Like many eukaryotic cells, muscle fibers possess a protein machinery ensuring fast resealing of damaged plasma membrane. Members of the annexins A (ANXA) family belong to this protein machinery. ANXA are small soluble proteins, twelve in number in humans, which share the property of binding to membranes exposing negatively-charged phospholipids in the presence of calcium (Ca2+). Many ANXA have been reported to participate in membrane repair of varied cell types and species, including human skeletal muscle cells in which they may play a collective role in protection and repair of the sarcolemma. Here, we discuss the participation of ANXA in membrane repair of healthy skeletal muscle cells and how dysregulation of ANXA expression may impact the clinical severity of muscular dystrophies.


Assuntos
Anexinas/metabolismo , Proteínas de Membrana/metabolismo , Distrofias Musculares/metabolismo , Anexina A1/metabolismo , Anexina A1/fisiologia , Anexinas/fisiologia , Membrana Celular/metabolismo , Humanos , Fibras Musculares Esqueléticas/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Distrofias Musculares/fisiopatologia
4.
J Colloid Interface Sci ; 600: 854-864, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34052534

RESUMO

HYPOTHESIS: Annexin A4 and A5 (ANXA4, ANXA5), both shown to be required for efficient plasma membrane repair (PMR) in living cells, bind as trimers to anionic membranes in the presence of calcium. Both annexins induce membrane curvature and self-assemble into crystal arrays on membranes, observations that have been associated with PMR. However, in-vitro studies of annexins have traditionally been performed using single annexins, despite the recruitment of multiple annexins to the damage site in cells. Hence, we study the potential cooperativity of ANXA4 and ANXA5 during membrane binding. EXPERIMENTS: Laser injury experiments were performed on MCF7 cells transfected to transiently express labelled ANXA4 and ANXA5 to study the localization of the proteins at the damage site. Using free-edged DOPC/DOPS (9:1) membranes we investigated the annexin-induced membrane rolling by fluorescence microscopy and the lateral arrangement of annexin trimers on the membrane surface by atomic force microscopy (AFM). FINDING: ANXA4 and ANXA5 colocalise at the damage site of MCF7 cells during repair. A (1:1) mixture of ANXA4 and ANXA5 induces membrane rolling with a time constant intermediate between the value for the pure annexins. While binding of the pure annexins creates crystal lattices, the (1:1) mixture generates a random arrangement of trimers. Thus, curvature induction remains as a functional property of annexin mixtures in PMR rather than crystal formation.


Assuntos
Anexina A4 , Anexinas , Anexina A5 , Anexinas/genética , Cálcio/metabolismo , Membrana Celular/metabolismo
5.
Anticancer Res ; 41(3): 1349-1355, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33788726

RESUMO

BACKGROUND/AIM: Small bowel adenocarcinoma (SBA) is a relatively rare malignant epithelial neoplasm. Thus, little is known about prognostic biomarkers of SBA. Annexin A10 (ANXA10) is a member of the annexin family. The significance of ANXA10 expression in SBA is unclear. This is the first study to examine the expression of ANXA10 in SBA. MATERIALS AND METHODS: We immunohistochemically evaluated ANXA10 expression of SBA and studied the relationship between ANXA10 expression and clinicopathological factors. RESULTS: ANXA10 expression was detected in 17 (56.7%) of 30 SBA cases and was significantly associated with poor overall survival. Univariate predictors for poor prognosis were tumour size (p=0.017) and ANXA10 expression (p=0.026). In multivariate analysis, ANXA10 expression (p=0.038) and tumour size (p=0.024) were found to be independent predictors of poor prognosis. CONCLUSION: ANXA10 could be a new prognostic biomarker for SBA.


Assuntos
Adenocarcinoma/metabolismo , Anexinas/biossíntese , Biomarcadores Tumorais/biossíntese , Intestino Delgado/metabolismo , Adenocarcinoma/diagnóstico , Idoso , Feminino , Humanos , Imuno-Histoquímica/métodos , Intestino Delgado/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico
6.
Biochim Biophys Acta Mol Cell Res ; 1868(7): 118991, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33667528

RESUMO

Vascular endothelial cells are subject to mechanical stress resulting from blood flow and interactions with leukocytes. Stress occurs at the apical, vessel-facing cell surface and leads to membrane ruptures that have to be resealed to ensure cell survival. To mimic this process, we developed a laser ablation protocol selectively inducing wounds in the apical plasma membrane of endothelial cells. We show that Ca2+-dependent membrane resealing is initiated following this wounding protocol and that the process is accompanied by substantial membrane lipid dynamics at the wound site. Specifically, phosphatidylinositol (4,5)-bisphosphate, phosphatidylserine and phosphatidic acid rapidly accumulate at membrane wounds forming potential interaction platforms for Ca2+/phospholipid binding proteins of the annexin (Anx) family that are also recruited within seconds after wounding. Depletion of one annexin, AnxA2, and its putative binding partner S100A11 interferes with membrane resealing suggesting that Ca2+-dependent annexin-phospholipid interactions are required for efficient membrane wound repair in endothelial cells.


Assuntos
Membrana Celular/fisiologia , Cicatrização/fisiologia , Anexina A2/metabolismo , Anexinas/metabolismo , Membrana Celular/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Lipídeos de Membrana/metabolismo , Lipídeos de Membrana/fisiologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/fisiologia , Ácidos Fosfatídicos , Fosfatidilinositol 4,5-Difosfato , Fosfatidilserinas , Fosfolipídeos/metabolismo , Ligação Proteica , Proteínas S100/metabolismo
7.
Nat Plants ; 7(3): 342-352, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33633358

RESUMO

Plants use extracellular vesicles (EVs) to transport small RNAs (sRNAs) into their fungal pathogens and silence fungal virulence-related genes through a phenomenon called 'cross-kingdom RNAi'. It remains unknown, however, how sRNAs are selectively loaded into EVs. Here, we identified several RNA-binding proteins in Arabidopsis, including Argonaute 1 (AGO1), RNA helicases (RHs) and annexins (ANNs), which are secreted by exosome-like EVs. AGO1, RH11 and RH37 selectively bind to EV-enriched sRNAs but not to non-EV-associated sRNAs, suggesting that they contribute to the selective loading of sRNAs into EVs. Conversely, ANN1 and ANN2 bind to sRNAs non-specifically. The ago1, rh11 rh37 and ann1 ann2 mutants showed reduced secretion of sRNAs in EVs, demonstrating that these RNA-binding proteins play an important role in sRNA loading and/or stabilization in EVs. Furthermore, rh11 rh37 and ann1 ann2 showed increased susceptibility to Botrytis cinerea, suggesting that RH11, RH37, ANN1 and ANN2 positively regulate plant immunity against B. cinerea.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Vesículas Extracelulares/metabolismo , RNA de Plantas/metabolismo , Proteínas de Ligação a RNA/metabolismo , Anexinas/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Proteínas Argonauta/metabolismo , Botrytis , RNA Helicases DEAD-box/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Proteoma , RNA Interferente Pequeno , Tetraspaninas/metabolismo
8.
Stem Cell Res ; 52: 102246, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33610019

RESUMO

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and lower motor neurons, causing gradual paralysis, and resulting in death 3-5 years from diagnosis. ALS causative mutations have been identified in multiple genes, including Fused in sarcoma (FUS), and recently characterized Annexin A11 (ANXA11). We have derived induced pluripotent stem cell (iPSC) lines from six ALS patient lymphoblastoid cell lines, three with mutations in FUS (Q519E, R521H, R522G), and three with mutations in ANXA11 (G38R, D40G, R235Q). These lines have been characterized and provide a novel resource for investigation into ALS pathology.


Assuntos
Esclerose Amiotrófica Lateral , Células-Tronco Pluripotentes Induzidas , Esclerose Amiotrófica Lateral/genética , Anexinas/genética , Humanos , Neurônios Motores , Mutação/genética , Proteína FUS de Ligação a RNA/genética
9.
Parasit Vectors ; 14(1): 103, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557917

RESUMO

BACKGROUND: Cystic echinococcosis is a parasitic zoonotic disease, which poses a threat to public health and animal husbandry, and causes significant economic losses. Annexins are a family of phospholipid-binding proteins with calcium ion-binding activity, which have many functions. METHODS: Two annexin protein family genes [Echinococcus granulosus annexin B3 (EgAnxB3) and EgAnxB38] were cloned and molecularly characterized using bioinformatic analysis. The immunoreactivity of recombinant EgAnxB3 (rEgAnxB3) and rEgAnxB38 was investigated using western blotting. The distribution of EgAnxB3 and EgAnxB38 in protoscoleces (PSCs), the germinal layer, 18-day strobilated worms and 45-day adult worms was analyzed by immunofluorescence localization, and their secretory characteristics were analyzed preliminarily; in addition, quantitative real-time reverse transcription polymerase chain reaction was used to analyze their transcript levels in PSCs and 28-day strobilated worms stages. The phospholipid-binding activities of rEgAnxB3 and rEgAnxB38 were also analyzed. RESULTS: EgAnxB3 and EgAnxB38 are conserved and contain calcium-binding sites. Both rEgAnxB3 and rEgAnxB38 could be specifically recognized by the serum samples from E. granulosus-infected sheep, indicating that they had strong immunoreactivity. EgAnxB3 and EgAnxB38 were distributed in all stages of E. granulosus, and their transcript levels were high in the 28-day strobilated worms. They were found in liver tissues near the cysts. In addition, rEgAnxB3 has Ca2+-dependent phospholipid-binding properties. CONCLUSIONS: EgAnxB3 and EgAnxB38 contain calcium-binding sites, and rEgAnxB3 has Ca2+-dependent phospholipid-binding properties. EgAnxB3 and EgAnxB38 were transcribed in PSCs and 28-day strobilated worms. They were expressed in all stages of E. granulosus, and distributed in the liver tissues near the hydatid cyst, indicating that they are secreted proteins that play a crucial role in the development of E. granulosus.


Assuntos
Anexinas/classificação , Anexinas/genética , Echinococcus granulosus/genética , Sequência de Aminoácidos , Animais , Anexinas/química , Clonagem Molecular , Biologia Computacional , Cães , Equinococose/parasitologia , Feminino , Masculino , Ligação Proteica , Coelhos , Alinhamento de Sequência , Ovinos
10.
Nat Commun ; 12(1): 1085, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597515

RESUMO

Liquid-liquid phase separation of proteins underpins the formation of membraneless compartments in living cells. Elucidating the molecular driving forces underlying protein phase transitions is therefore a key objective for understanding biological function and malfunction. Here we show that cellular proteins, which form condensates at low salt concentrations, including FUS, TDP-43, Brd4, Sox2, and Annexin A11, can reenter a phase-separated regime at high salt concentrations. By bringing together experiments and simulations, we demonstrate that this reentrant phase transition in the high-salt regime is driven by hydrophobic and non-ionic interactions, and is mechanistically distinct from the low-salt regime, where condensates are additionally stabilized by electrostatic forces. Our work thus sheds light on the cooperation of hydrophobic and non-ionic interactions as general driving forces in the condensation process, with important implications for aberrant function, druggability, and material properties of biomolecular condensates.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Transição de Fase , Proteínas/química , Eletricidade Estática , Animais , Anexinas/química , Proteínas de Ciclo Celular/química , Proteínas de Ligação a DNA/química , Humanos , Proteína FUS de Ligação a RNA/química , Fatores de Transcrição SOXB1/química , Células Sf9 , Spodoptera , Fatores de Transcrição/química
11.
J Cell Biol ; 220(3)2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33496727

RESUMO

Mutations in ANO5 (TMEM16E) cause limb-girdle muscular dystrophy R12. Defective plasma membrane repair is a likely mechanism. Using myofibers from Ano5 knockout mice, we show that trafficking of several annexin proteins, which together form a cap at the site of injury, is altered upon loss of ANO5. Annexin A2 accumulates at the wound to nearly twice the level observed in WT fibers, while annexin A6 accumulation is substantially inhibited in the absence of ANO5. Appearance of annexins A1 and A5 at the cap is likewise diminished in the Ano5 knockout. These changes are correlated with an alteration in annexin repair cap fine structure and shedding of annexin-positive vesicles. We conclude that loss of annexin coordination during repair is disrupted in Ano5 knockout mice and underlies the defective repair phenotype. Although ANO5 is a phospholipid scramblase, abnormal repair is rescued by overexpression of a scramblase-defective ANO5 mutant, suggesting a novel, scramblase-independent role of ANO5 in repair.


Assuntos
Anexinas/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Animais , Anoctaminas/química , Anoctaminas/deficiência , Anoctaminas/genética , Anoctaminas/metabolismo , Cálcio/metabolismo , Membrana Celular/metabolismo , Células Cultivadas , Humanos , Cinética , Camundongos Knockout , Mutação/genética , Fosfatidiletanolaminas/metabolismo , Fosfatidilserinas/metabolismo , Domínios Proteicos , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
12.
Int J Mol Sci ; 22(2)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33419052

RESUMO

Extracellular ATP (eATP) has long been established in animals as an important signalling molecule but this is less understood in plants. The identification of Arabidopsis thaliana DORN1 (Does Not Respond to Nucleotides) as the first plant eATP receptor has shown that it is fundamental to the elevation of cytosolic free Ca2+ ([Ca2+]cyt) as a possible second messenger. eATP causes other downstream responses such as increase in reactive oxygen species (ROS) and nitric oxide, plus changes in gene expression. The plasma membrane Ca2+ influx channels involved in eATP-induced [Ca2+]cyt increase remain unknown at the genetic level. Arabidopsis thaliana Annexin 1 has been found to mediate ROS-activated Ca2+ influx in root epidermis, consistent with its operating as a transport pathway. In this study, the loss of function Annexin 1 mutant was found to have impaired [Ca2+]cyt elevation in roots in response to eATP or eADP. Additionally, this annexin was implicated in modulating eATP-induced intracellular ROS accumulation in roots as well as expression of eATP-responsive genes.


Assuntos
Trifosfato de Adenosina/metabolismo , Anexinas/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cálcio/metabolismo , Raízes de Plantas/metabolismo , Difosfato de Adenosina/metabolismo , Anexinas/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Citosol/metabolismo , Espaço Extracelular/metabolismo , Regulação da Expressão Gênica de Plantas , Liases/genética , Liases/metabolismo , Mutação , Raízes de Plantas/genética , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Mecânico , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Ir J Med Sci ; 190(1): 59-65, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32451762

RESUMO

BACKGROUND: The incidence of thyroid cancer (TC) is increasing rapidly worldwide. The target therapy for papillary TC (PTC) is limited, and the studies of PTC prognostic biomarkers are not common. As a new member of annexin A (ANXA) family, the function and clinical significance of ANXA10 in PTC have not been well investigated. METHODS: Expressions of all the 12 ANXA members were detected with qPCR in 12 PTC tissues, and the ANXA10 mRNAs in PTCs and their adjacent normal thyroid tissues were compared. The subcellular location and expression of ANXA10 in 121 PTC patients were investigated with immunohistochemistry, which further classified the patients into subgroups with low or high ANXA10. The clinical significance and prognostic value of ANXA10 were estimated by analyzing its correlation with clinical factors and overall survival rates by the chi-squared test, univariate analyses, and multivariate analyses. RESULTS: ANXA10 had the highest expression in PTCs among all the ANXA members. Moreover, ANXA10 was significantly upregulated in PTC compared with normal thyroid tissues. The PTC patients with low and high expression of ANXA10 took up 70.25% (85/121) and 29.75% (36/121), respectively. ANXA10 expression was associated with tumor size, differentiation, and overall survival rates of PTC. ANXA10 was an independent prognostic biomarker predicting the poor outcome of PTC. CONCLUSIONS: ANXA10 expression was upregulated in PTC, and it was an independent prognostic biomarker of PTC, suggesting that ANXA10 may be a promising target for individual treatment of ANXA10.


Assuntos
Anexinas/sangue , Biomarcadores Tumorais/metabolismo , Câncer Papilífero da Tireoide/diagnóstico , Biomarcadores Tumorais/biossíntese , Linhagem Celular Tumoral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Câncer Papilífero da Tireoide/sangue
14.
Med Hypotheses ; 144: 110286, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33254588

RESUMO

Neoplastic cells hijack cell death pathways to evade the immune response. Phosphatidylserine, a marker of apoptotic cells, and its highly conserved bridging proteins, annexins and ß2-glycoprotein I, facilitate the efficient removal of apoptotic and necrotic cells via tumor-associated phagocytes in a process called efferocytosis. Efferocytosis results in the clearance of dead and dying cells and local immune suppression. Neoplastic cells also have an increased capacity to activate complement. Complement may facilitate the silent removal of tumor cells and has a dual role in promoting and inhibiting tumor growth. Here I hypothesize that immune response-generating IgG autoantibodies that recognize opsonizing fragments C1q, C3b, and phosphatidylserine-binding proteins (annexins, ß2-glycoprotein I) may reduce tumor growth. I propose that these autoantibodies induce a pro-inflammatory, cytotoxic tumor microenvironment. Further, I predict that autoantibodies can drive neoplastic cell phagocytosis in an Fc receptor-dependent manner and recruit additional complement, resulting in immune-stimulatory effects. Excessive complement activation and antibody-dependent cytotoxicity may stimulate anti-tumor responses, including damage to tumor vasculature. Here I provide insights that may aid the development of more effective therapeutic modalities to control cancer. Such therapeutic approaches should kill neoplastic cells and target their interaction with host immune cells. Thereby the pro-tumorigenic effect of dead cancer cells could be limited while inducing the anti-tumor potential of tumor-associated phagocytes.


Assuntos
Autoanticorpos , Complemento C1q , Anexinas , Apoptose , Complemento C1q/metabolismo , Fagocitose , beta 2-Glicoproteína I
15.
Cells ; 9(11)2020 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-33202541

RESUMO

Discovered over 40 years ago, the annexin proteins were found to be a structurally conserved subgroup of Ca2+-binding proteins. While the initial research on annexins focused on their signature feature of Ca2+-dependent binding to membranes, over the years the biennial Annexin conference series has highlighted additional diversity in the functions attributed to the annexin family of proteins. The roles of these proteins now extend from basic science to biomedical research, and are being translated into the clinic. The research on annexins involves a global network of researchers, and the 10th biennial Annexin conference brought together over 80 researchers from ten European countries, USA, Brazil, Singapore, Japan and Australia for 3 days in September 2019. In this conference, the discussions focused on two distinct themes-the role of annexins in cellular organization and in health and disease. The articles published in this Special Issue cover these two main themes discussed at this conference, offering a glimpse into some of the notable findings in the field of annexin biology.


Assuntos
Anexinas/metabolismo , Animais , Autofagia , Doença , Saúde , Interações Hospedeiro-Patógeno , Humanos , Inflamação/patologia , Neoplasias de Mama Triplo Negativas/patologia
16.
Dokl Biochem Biophys ; 494(1): 219-221, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33119820

RESUMO

In the present study, we assessed the role of annexin 13 membrane-binding protein (ANXA13) in the intracellular transport of vesicles containing type II ribosome-inactivating proteins (RIP-IIs). A modified human intestinal epithelial cell line HT29 was used, in which the expression of ANXA13 was significantly reduced. The cytotoxic effect of ricin and viscumin was evaluated by modification of 28S ribosome RNA. The observed differences in the activity of toxins on the parental and modified HT29 lines indicate that ANXA13 plays a different role in the intracellular transport of vesicles containing the RIP-IIs.


Assuntos
Anexinas/metabolismo , Substâncias para a Guerra Química/farmacologia , Neoplasias do Colo/patologia , Proteínas Inativadoras de Ribossomos Tipo 2/farmacologia , Proteínas Inativadoras de Ribossomos/metabolismo , Ribossomos/efeitos dos fármacos , Ricina/farmacologia , Toxinas Biológicas/farmacologia , Transporte Biológico , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Células HT29 , Humanos
17.
Sci Transl Med ; 12(566)2020 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087501

RESUMO

Dysregulation of calcium ion homeostasis and abnormal protein aggregation have been proposed as major pathogenic hallmarks underpinning selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). Recently, mutations in annexin A11 (ANXA11), a gene encoding a Ca2+-dependent phospholipid-binding protein, have been identified in familial and sporadic ALS. However, the physiological and pathophysiological roles of ANXA11 remain unknown. Here, we report functions of ANXA11 related to intracellular Ca2+ homeostasis and stress granule dynamics. We analyzed the exome sequences of 500 Korean patients with sALS and identified nine ANXA11 variants in 13 patients. The amino-terminal variants p.G38R and p.D40G within the low-complexity domain of ANXA11 enhanced aggregation propensity, whereas the carboxyl-terminal ANX domain variants p.H390P and p.R456H altered Ca2+ responses. Furthermore, all four variants in ANXA11 underwent abnormal phase separation to form droplets with aggregates and led to the alteration of the biophysical properties of ANXA11. These functional defects caused by ALS-linked variants induced alterations in both intracellular Ca2+ homeostasis and stress granule disassembly. We also revealed that p.G228Lfs*29 reduced ANXA11 expression and impaired Ca2+ homeostasis, as caused by missense variants. Ca2+-dependent interaction and coaggregation between ANXA11 and ALS-causative RNA-binding proteins, FUS and hnRNPA1, were observed in motor neuron cells and brain from a patient with ALS-FUS. The expression of ALS-linked ANXA11 variants in motor neuron cells caused cytoplasmic sequestration of endogenous FUS and triggered neuronal apoptosis. Together, our findings suggest that disease-associated ANXA11 mutations can contribute to ALS pathogenesis through toxic gain-of-function mechanisms involving abnormal protein aggregation.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/genética , Anexinas/genética , Cálcio , Homeostase , Humanos , Mutação/genética
18.
Food Funct ; 11(10): 8866-8877, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32985639

RESUMO

Chrysanthemum has been viewed as an important traditional Chinese medicine (TCM) with a long history. Research studies indicated many potential pharmaceutical effects of chrysanthemum extract. However, hardly any investigation has been performed to describe its toxicity. In this study, acute application of chrysanthemum ethanol extract (CEE, 300 mg kg-1) was found to induce apoptosis of hepatic Kupffer cells in vivo. CEE was also observed to induce apoptosis of RAW264.7 cells in a dose- and time-dependent manner. Further analysis using flow cytometry and western blotting revealed that CEE induced apoptosis of RAW264.7 cells via a mitochondria-dependent pathway. After a HPLC combined screening assay, we narrowed down the toxicity caused by the petroleum extract of CEE (CEE-PE, 66 µg mL-1). In vivo effects of CEE-PE were also tested in mice. Additionally, nine potential toxic compounds were isolated and identified from CEE-PE. In all, we found that components with small polarities in CEE could induce apoptosis of Kupffer cells and macrophages via a mitochondrial dependent pathway, which might draw attention to the safety issues of everyday use of chrysanthemum.


Assuntos
Apoptose/efeitos dos fármacos , Chrysanthemum/química , Macrófagos do Fígado/efeitos dos fármacos , Mitocôndrias/metabolismo , Extratos Vegetais/farmacologia , Animais , Anexinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Chrysanthemum/efeitos adversos , Etanol/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Modelos Animais , Extratos Vegetais/toxicidade , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
19.
Int J Mol Sci ; 21(16)2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32824294

RESUMO

Annexins and S100 proteins form two large families of Ca2+-binding proteins. They are quite different both structurally and functionally, with S100 proteins being small (10-12 kDa) acidic regulatory proteins from the EF-hand superfamily of Ca2+-binding proteins, and with annexins being at least three-fold larger (329 ± 12 versus 98 ± 7 residues) and using non-EF-hand-based mechanism for calcium binding. Members of both families have multiple biological roles, being able to bind to a large cohort of partners and possessing a multitude of functions. Furthermore, annexins and S100 proteins can interact with each other in either a Ca2+-dependent or Ca2+-independent manner, forming functional annexin-S100 complexes. Such functional polymorphism and binding indiscrimination are rather unexpected, since structural information is available for many annexins and S100 proteins, which therefore are considered as ordered proteins that should follow the classical "one protein-one structure-one function" model. On the other hand, the ability to be engaged in a wide range of interactions with multiple, often unrelated, binding partners and possess multiple functions represent characteristic features of intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs); i.e., functional proteins or protein regions lacking unique tertiary structures. The aim of this paper is to provide an overview of the functional roles of human annexins and S100 proteins, and to use the protein intrinsic disorder perspective to explain their exceptional multifunctionality and binding promiscuity.


Assuntos
Anexinas/metabolismo , Mapas de Interação de Proteínas , Proteínas S100/metabolismo , Anexinas/química , Humanos , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/metabolismo , Ligação Proteica , Proteínas S100/química
20.
Biomed Pharmacother ; 130: 110591, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32763821

RESUMO

Annexin A is a kind of calcium-dependent phospholipid-binding proteins, which contributes to the formation of the cell membranes and cytoskeleton and played a part as a membrane skeleton to stabilize lipid bilayer. Autophagy is one of the most important programmed cell death mechanisms. And recently some reports suggest that annexin A family protein is associated with autophagy for annexin A can regulate the formation of vesicular lipid membranes and promote cell exocytosis. In this review, we summarized the roles of annexin A protein family in autophagy regulation and targeted medical treatment for better diagnoses and therapies.


Assuntos
Anexinas/genética , Anexinas/fisiologia , Autofagia/genética , Autofagia/fisiologia , Neoplasias/tratamento farmacológico , Neoplasias/genética , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/genética , Animais , Humanos
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