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1.
BMC Complement Med Ther ; 23(1): 200, 2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37330478

RESUMO

BACKGROUND: Chronic heart failure (CHF) is actually a disease caused by an imbalanced energy metabolism between myocardial energy demand and supply, ultimately resulting in abnormal myocardial cell structure and function. Energy metabolism imbalance plays an important role in the pathological process of chronic heart failure (CHF). Improving myocardial energy metabolism is a new strategy for the treatment of CHF. Shengxian decoction (SXT), a well-known traditional Chinese medicine (TCM) formula, has good therapeutic effects on the cardiovascular system. However, the effects of SXT on the energy metabolism of CHF is unclear. In this study, we probed the regulating effects of SXT on energy metabolism in CHF rats using various research methods. METHODS: High-performance liquid chromatography (HPLC) analysis was used to perform quality control of SXT preparations. Then, SD rats were randomly assigned into 6 groups: sham, model, positive control (trimetazidine) and high-, middle-, and low-dose SXT groups. Specific reagent kits were used to detect the expression levels of ALT and AST in rats' serum. Echocardiography was used to evaluate cardiac function. H&E, Masson and TUNEL staining were performed to examine myocardial structure and myocardial apoptosis. Colorimetry was used to determine myocardial ATP levels in experimental rats. Transmission electron microscopy was used to observe the ultrastructure of myocardial mitochondria. ELISA was used to estimate CK, cTnI, and NT-proBNP levels, and LA、FFA、MDA、SOD levels. Finally, Western blotting was used to examine the protein expression of CPT-1, GLUT4, AMPK, p-AMPK, PGC-1α, NRF1, mtTFA and ATP5D in the myocardium. RESULTS: HPLC showed that our SXT preparation method was feasible. The results of ALT and AST tests indicate that SXT has no side effect on the liver function of rats. Treatment with SXT improved cardiac function and ventricular remodelling and inhibited cardiomyocyte apoptosis and oxidative stress levels induced by CHF. Moreover, CHF caused decrease ATP synthesis, which was accompanied by a reduction in ATP 5D protein levels, damage to mitochondrial structure, abnormal glucose and lipid metabolism, and changes in the expression of PGC-1α related signal pathway proteins, all of which were significantly alleviated by treatment with SXT. CONCLUSION: SXT reverses CHF-induced cardiac dysfunction and maintains the integrity of myocardial structure by regulating energy metabolism. The beneficial effect of SXT on energy metabolism may be related to regulating the expression of the PGC-1α signalling pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Insuficiência Cardíaca , Ratos , Animais , Ratos Sprague-Dawley , Proteínas Quinases Ativadas por AMP/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Miocárdio/metabolismo , Trifosfato de Adenosina/metabolismo
2.
Artigo em Inglês | MEDLINE | ID: mdl-33548831

RESUMO

Pagiophloeus tsushimanus is a new, destructive, and monophagous weevil pest that thrives on Cinnamomum camphora, found in Shanghai. The functions of chemosensory genes involved in the host location and intraspecific communication of P. tsushimanus remain unknown. The male-female transcriptomes of P. tsushimanus adults were assembled using Illumina sequencing, and we focused on all chemosensory genes in transcriptomes. In general, 58,088 unigenes with a mean length of 1018.19 bp were obtained. In total, 39 odorant binding proteins (OBPs), 10 chemosensory proteins (CSPs), 22 olfactory receptors (ORs), 16 gustatory receptors (GRs), eight ionotropic receptors (IRs), and five sensory neuron membrane proteins (SNMPs) were identified. PtsuOBPs comprised four subfamilies (20 Minus-C, one Plus-C, two Dimer, and 15 Classic). Both PtsuOBPs and PtsuCSPs contained a highly conserved sequence motif of cysteine residues. PtsuORs including one olfactory receptor co-receptors (Ptsu/Orco) comprised seven predicted transmembrane domains. Phylogenetic analysis revealed that PtsuOBPs, PtsuCSPs, and PtsuORs in P. tsushimanus exhibited low homology compared to other insect species. The results of tissue- and sex-specific expression patterns indicated that PtsuOBPs and PtsuORs were highly abundant in the antennae; whereas, PtsuCSPs were not only highly abundant in antennae, but also abdominal apexes, wings, and legs. In conclusion, these results enrich the gene database of P. tsushimanus, which may serve as a basis for identifying novel targets to disrupt olfactory key genes and may provide a reverse validation method to identify attractants for formulating potential eco-friendly control strategies for this pest.


Assuntos
Transcriptoma , Gorgulhos/genética , Animais , Cinnamomum camphora/parasitologia , Feminino , Proteínas de Insetos/genética , Canais Iônicos de Abertura Ativada por Ligante/genética , Masculino , Proteínas de Membrana/genética , Filogenia , Receptores Odorantes/genética , Células Receptoras Sensoriais/metabolismo , Gorgulhos/citologia
3.
Biochem Biophys Res Commun ; 495(4): 2475-2481, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29278700

RESUMO

Myocardial ischemia/reperfusion (I/R) still have high morbidity and mortality worldwide. Platelet activating factor (PAF) is a potent phospholipid regulator of inflammation. PAF acts on a single receptor (PAFR), which is expressed on cellular and nuclear membranes of various cell types. The study is aimed to explore if PAFR could modulate myocardial I/R injury in mice. PAFR expressions began to up-regulate at 1 h, and reached peak at 24 h. PAFR deletion markedly attenuated myocardial I/R injury, evidenced by the reduced infarct size and the improved cardiac function. Furthermore, PAFR-knockout inhibited inflammatory response, as demonstrated by down-regulated pro-inflammatory cytokines and chemokine, as well as the inactivation of nuclear factor κB (NF-κB). Additionally, PAFR-absence ameliorated oxidative stress induced by myocardial I/R, associated with the up-regulation of superoxide dismutase (SOD) and nuclear respiratory factor 2 (Nrf-2) activity. Finally, PAFR-deficiency impeded apoptosis, which was proved by the decreasing in terminal deoxynucleotidyl transferase (TdT)-mediated dNTP nick end labeling (TUNEL)-positive myocytes, and Caspase-3 cleavage. And the activation of Janus kinase 1-signal transducer and activator of transcription 1 (JAK1/STAT1) pathway was also suppressed by PAFR-knockout. The findings above were confirmed in lipopolysaccharide (LPS)-incubated cardiomyocytes with or without PAFR expressions in vitro. In summary, we supposed that inhibiting PAFR reduced inflammation, oxidative stress and apoptosis, and thus might be a promising therapeutic strategy to alleviate myocardial I/R injury.


Assuntos
Apoptose/imunologia , Traumatismo por Reperfusão Miocárdica/imunologia , Miocardite/imunologia , Estresse Oxidativo/imunologia , Animais , Citocinas/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismo por Reperfusão Miocárdica/patologia , Miocardite/patologia , Glicoproteínas da Membrana de Plaquetas/genética , Glicoproteínas da Membrana de Plaquetas/imunologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/imunologia
4.
Steroids ; 123: 20-26, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28483508

RESUMO

A series of 4'-acylamino modified Δ1,4-pregnadien-21E-benzylidene-3,20-dione derivatives (6a-v) was synthesized from the commercially available progesterone (1). These title compounds were evaluated for their toxicity against brine shrimp (Artemia salina) and cytotoxic activities against two human cancer cell lines (HeLa and MCF-7). The results revealed that compound 6f exhibited promising in vitro cytotoxic activity to the two cancer cell lines and the nature of acylamino functional group in the benzylidene moiety had a significant influence on cytotoxicity.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Pregnadienos/síntese química , Pregnadienos/farmacologia , Animais , Antineoplásicos/química , Artemia/efeitos dos fármacos , Técnicas de Química Sintética , Células HeLa , Humanos , Células MCF-7 , Pregnadienos/química , Pregnadienos/toxicidade
5.
Toxicol In Vitro ; 35: 112-20, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27262408

RESUMO

Initiation of apoptosis is an important event for chemoprevention and chemotherapy of cancer. Naturally derived products had drawn growing attention as lead compounds for anticancer drug discovery. ABL-L, a semisynthetic analogue of natural sesquiterpenoid 1-O-acetylbritannilactone (ABL) isolated from Inula britannica, showed stronger suppression against three solid tumor cell lines with 4-10 fold improvement than ABL. However, its molecular mechanism of cell death induction has still not been determined. The present study evaluated the anticancer efficacy of ABL-L and its biological activities mechanism on human laryngocarcinoma cells HEp-2 in vitro. We found that ABL-L-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest. Typical apoptotic morphological and biochemical features were also observed in treated cells. Furthermore, the levels of the anti-apoptotic Bcl-2, pro-caspase 3/8/9 and poly(ADP-ribose) polymerase PARP decreased, and the level of pro-apoptotic Bax increased. Involvement of the caspase-mediated apoptosis was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. In addition, ABL-L induced a tumor suppressor p53 and its target genes expression p21, fas, noxa and puma. The results of p53 knockdown suggest that caspase-mediated apoptosis induced by ABL-L was in p53-dependent pathway on HEp-2 cells. Our data indicate that the cytotoxicity of the novel semisynthetic analogue ABL-L involved G1 cell cycle arrest and apoptosis via a p53-dependent, caspase-mediated pathway on human laryngocarcinoma cells.


Assuntos
Antineoplásicos/farmacologia , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Humanos , Neoplasias Laríngeas , Proteína Supressora de Tumor p53/genética
6.
Nat Prod Commun ; 11(1): 7-10, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26996005

RESUMO

In this study, five known sesquiterpene lactones (STL) with an α-methylene-γ-lactone motif, including two eudesmanolides, 1ß-hydroxyalantolactone (1) and ivangustin (2), and three 1,10-seco-eudesmanolides, 1-O-acetylbritannilactone (3), 1,6-O,O-diacetylbritannilactone (4), and 6α-O-(2- methylbutyryl)britannilactone (5) were isolated from the flower heads of the medicinal plant Inula britannica. Their structures were characterized by spectroscopic methods. X-ray data of 2 is reported for the first time. Among them, eudesmanolides 1 and 2 exhibited remarkable cytotoxicity against HEp2, SGC-7901 and HCT116 human cancer cell lines, comparable with etoposide (Vp-16) used as reference drug. Furthermore, treatment of HEp2 cells with 1 induced apoptosis associated with cleaved procaspase-3 and PARP. The biological assays carried out with normal cells (CHO) revealed that all sesquiterpenes were weakly selective against the cancer cell lines tested.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Inula/química , Sesquiterpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Flores/química , Humanos , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Sesquiterpenos/química
7.
J Plant Physiol ; 183: 64-74, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26092364

RESUMO

Expansins are cell wall proteins that are generally considered to be the key regulator of cell wall extension during plant growth. In this study, we used two different wheat (Triticum aestivum L.) cultivars to demonstrate that expansins are involved in wheat leaf growth and response to water stress, by regulating the expansin activity and cell wall susceptibility to expansins. Expansin activity was associated with the relative elongation rate of leaves during leaf development, suggesting their involvement in leaf elongation. Moreover, cell wall extension characteristics and expansin gene transcription were closely involved in the leaf cell elongation region. Water stress restrains leaf growth, but the growth rate of leaves was changed after rehydration, which is consistent with the response of expansin activity to water stress. Meanwhile, increased cell wall susceptibility to expansin by water deficit played an important role in maintaining cell wall extension. Furthermore, the expansin activity in drought-resistant cultivar HF9703 was always higher than that in drought-sensitive cultivar 921842 under water stress condition, which may be correlated with the higher expansin gene expression in HF9703 versus 921842. These data provide evidence for a role of expansins in the growth and response of wheat leaves to water stress.


Assuntos
Secas , Proteínas de Plantas/genética , Triticum/fisiologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Proteínas de Plantas/metabolismo , Triticum/genética , Triticum/crescimento & desenvolvimento
8.
Dalton Trans ; 43(37): 13924-31, 2014 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-25111133

RESUMO

Intensely luminescent 1,8-naphthyridine-BF2 complexes 1-9 containing terminal bidentate N^N^O and/or N^C^O groups are synthesized and structurally characterized by X-ray diffraction, electrospray ionization mass spectrometry, (1)H and (19)F NMR spectroscopy and elemental analysis. Complexes 1-4 are synthesized from 2-acetamino-1,8-naphthyridine derivatives by a facile route. Selective bonding modes and the chemical stability of complexes 5 and 6 obtained by reacting BF3·Et2O with 1,8-naphthyridine derivatives bearing dual-functional groups (N^C^O and N^N^O) are investigated by crystal structure analysis and time-dependent density functional theory calculations. The products containing a BF2 core bound to a N^C^O chelating group are energetically favorable and can expand the range of derivatives by substitution at the 2-position. In this regard, a free -NH2 group at the 2-position of complex 7 obtained from 5 can be functionalized under a variety of pH conditions to generate complexes 8 and 9, which bear flexible coordination arms that can be used to recognize certain transition metals. The photophysical properties of the complexes are examined in solution and solid state at room temperature. Compared with those of the starting naphthyridine-based compounds, the naphthyridine-BF2 complexes display desirable light-absorbing properties and intense solution and solid-state emission with large Stokes shifts. Complex 4 in solution exhibited an emission quantum yield of 0.98. In complexes 5-9, the binding sites for the BF2 core change from N^N^O to N^C^O, which leads to red shifts of absorption and emission, excellent chemical stability and high emission quantum yields.

9.
Plant Physiol Biochem ; 78: 53-62, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24636907

RESUMO

Phosphorus (P) is a critical macronutrient required for numerous functions in plants and is one of the limiting factors for plant growth. Phosphate availability has a strong effect on root system architecture. Expansins are encoded by a superfamily of genes that are organized into four families, and growing evidence has demonstrated that expansins are involved in almost all aspects of plant development, especially root development. In the current study, we demonstrate that expansins may be involved in increasing phosphorus availability by regulating the growth and development of plant roots. Multiple expansins (five α- and nine ß-expansin genes) were up- or down-regulated in response to phosphorus and showed different expression patterns in wheat. Meanwhile, the expression level of TaEXPB23 was up-regulated at excess-P condition, suggesting the involvement of TaEXPB23 in phosphorus adaptability. Overexpression of the TaEXPB23 resulted in improved phenotypes, particularly improved root system architecture, as indicated by the increased number of lateral roots in transgenic tobacco plants under excess-P and low-P conditions. Thus, these transgenic plants maintained better photosynthetic gas exchange ability than the control under both P-sufficient and P-deficient conditions.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Fósforo/farmacologia , Proteínas de Plantas/genética , Triticum/genética , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/genética , Biomassa , Relação Dose-Resposta a Droga , Família Multigênica , Fósforo/metabolismo , Fotossíntese/efeitos dos fármacos , Fotossíntese/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Brotos de Planta/genética , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/metabolismo , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Triticum/crescimento & desenvolvimento , Triticum/metabolismo
10.
Biochem Pharmacol ; 86(9): 1254-62, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23962446

RESUMO

Antibacterial peptides (ABPs) with cancer-selective toxicity have received much more attention as alternative chemotherapeutic agents in recent years. However, the basis of their anticancer activity remains unclear. The modification of cell surface glycosylation is a characteristic of cancer cells. The present study investigated the effect of glycosylation, in particular sialic acid, on the anticancer activity of ABPs. We showed that aurein 1.2, buforin IIb and BMAP-28m exhibited selective cytotoxicity toward MX-1 and MCF-7 breast cancer cells. The binding activity, cytotoxicity and apoptotic activity of ABPs were enhanced by the presence of O-, N-glycoproteins, gangliosides and sialic acid on the surface of breast cancer cells. Among N-, O-glycoproteins and ganglioside, O-glycoproteins almost had the strongest effect on the binding and cytotoxicity of the three peptides. Further, up-regulation of hST6Gal1 in CHO-K1 cells enhanced the susceptibility of cells to these peptides. Finally, the growth of MX-1 xenograft tumors in mice was significantly suppressed by buforin IIb treatment, which was associated with induction of apoptosis and inhibition of vascularization. These data demonstrate that the three peptides bind to breast cancer cells via an interaction with surface O-, N-glycoproteins and gangliosides. Sialic acids act as key glycan binding sites for cationic ABP binding to glycoproteins and gangliosides. Therefore, glycosylation in breast cancer cells plays an important role in the anticancer activity of ABPs, which may partly explain their cancer-selective toxicity. Anticancer ABPs with cancer-selective cytotoxicity will be promising candidates for anticancer therapy in the future.


Assuntos
Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Peptídeos/farmacologia , Animais , Peptídeos Catiônicos Antimicrobianos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Células CHO/efeitos dos fármacos , Cricetulus , Feminino , Gangliosídeos/metabolismo , Glicoproteínas/metabolismo , Glicosilação/efeitos dos fármacos , Humanos , Células MCF-7/efeitos dos fármacos , Camundongos , Camundongos Nus , Ácido N-Acetilneuramínico/metabolismo , Peptídeos/metabolismo , Proteínas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Plant Physiol Biochem ; 54: 49-58, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22381655

RESUMO

Expansins are proteins that are generally accepted to be key regulators of cell wall extension and plant growth. We examined the expression pattern of TaEXPB23, a wheat (Triticum aestivum L.) expansin gene, under exogenous phytohormone and abiotic stress treatments. In addition, we evaluated its function in the tolerance to salt stress and high temperature (HT) by overexpressing it in transgenic tobacco plants. In subcellular localization assays, TaEXPB23 localized to the cell wall. Expression analysis demonstrated that the transcription pattern of TaEXPB23 corresponded to wheat coleoptile growth. Real-time RT-PCR analysis revealed that TaEXPB23 transcript expression was upregulated by exogenous methyl jasmonate (MeJA) and salt stress, but downregulated by exogenous gibberellins (GA3), ethylene (ET), indole-3-acetic acid (IAA) and α-naphthlcetic acid (NAA). Overexpression of TaEXPB23 in tobacco (tabacum) conferred tolerance to salt stress by enhancing water retention ability (WRA) and decreasing osmotic potential (OP). However, transgenic plants overexpressing TaEXPB23 did not show any improvement in the tolerance to HT stress. These results suggested that TaEXPB23 is regulated by phytohormones and is involved in the regulation of salt stress tolerance.


Assuntos
Adaptação Fisiológica/genética , Genes de Plantas , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Tolerância ao Sal/genética , Estresse Fisiológico/genética , Triticum/genética , Temperatura Alta , Osmose , Plantas Geneticamente Modificadas , Cloreto de Sódio/efeitos adversos , Nicotiana/genética , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Regulação para Cima , Água/metabolismo
12.
Amino Acids ; 42(6): 2393-402, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21805135

RESUMO

The increasing resistance of bacteria and fungi to currently available antibiotics is a major concern worldwide, leading to enormous efforts to develop new antibiotics with new modes of actions. Antibacterial peptide CM4 (ABP-CM4) is a small cationic peptide with broad-spectrum activities against bacteria, fungi, and tumor cells, which may possibly be used as a promising candidate for a new antibiotic. For pharmaceutical applications, a large quantity of antimicrobial peptides needs to be produced economically. In this communication, the progress in the structural characteristics, heterologous production, and biological evaluation of ABP-CM4 are reviewed.


Assuntos
Peptídeos Catiônicos Antimicrobianos/biossíntese , Proteínas Recombinantes de Fusão/biossíntese , Sequência de Aminoácidos , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Dicroísmo Circular , Clonagem Molecular , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Fungos/efeitos dos fármacos , Expressão Gênica , Humanos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Dados de Sequência Molecular , Pichia/genética , Pichia/metabolismo , Estrutura Secundária de Proteína , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/farmacologia
13.
Plant Cell Rep ; 31(4): 671-85, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22076248

RESUMO

Expansin protein is a component of the cell wall generally accepted to be the key regulator of cell wall extension during plant growth. Plant hormones regulate expansin gene expression as well as plant growth during drought stress. However, the relationship between expansin and plant hormone is far from clear. Here, we studied the involvement of expansin in plant cell growth mediated by the hormones indole-3-acetic acid (IAA) and abscisic acid (ABA) under osmotic stress which was induced by polyethylene glycol (PEG)-6000. Wheat coleoptiles from a drought-resistant cultivar HF9703 and a drought-sensitive cultivar 921842 were used to evaluate cell growth and expansin activity. Osmotic stress induced the accumulation of ABA. ABA induced expansin activity mainly by enhancing expansin expression, since ABA induced cell wall basification via decreasing plasma membrane H(+)-ATPase activity, which was unfavorable for expansin activity. Although ABA induced expansin activity and cell wall extension, treatment with exogenous ABA and/or fluridone (FLU, an ABA inhibitor) suggested that ABA was involved in the coleoptile growth inhibition during osmotic stress. IAA application to detached coleoptiles also enhanced coleoptile growth and increased expansin activity, but unlike ABA, IAA-induced expansin activity was mainly due to the decrease of cell wall pH by increasing plasma membrane H(+)-ATPase activity. Compared with drought-sensitive cultivar, the drought-resistant cultivar could maintain greater expansin activity and cell wall extension, which was contributive to its resultant faster growth under water stress.


Assuntos
Ácido Abscísico/farmacologia , Ácidos Indolacéticos/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/metabolismo , Triticum/fisiologia , Ácido Abscísico/antagonistas & inibidores , Ácido Abscísico/metabolismo , Membrana Celular/enzimologia , Parede Celular/metabolismo , Cotilédone/genética , Cotilédone/crescimento & desenvolvimento , Cotilédone/fisiologia , Desidratação , Secas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/fisiologia , Herbicidas/farmacologia , Concentração de Íons de Hidrogênio , Ácidos Indolacéticos/metabolismo , Pressão Osmótica/efeitos dos fármacos , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Polietilenoglicóis/farmacologia , ATPases Translocadoras de Prótons/metabolismo , Piridonas/farmacologia , RNA de Plantas/genética , Fatores de Tempo , Triticum/efeitos dos fármacos , Triticum/genética , Triticum/crescimento & desenvolvimento , Água/metabolismo
14.
Peptides ; 31(8): 1504-10, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20493915

RESUMO

Some cationic antibacterial peptides exhibit a broad spectrum of cytotoxic activity against cancer cells, which could provide a new class of anticancer drugs. In the present study, the anticancer activity of ABP-CM4, an antibacterial peptide from Bombyx mori, against leukemic cell lines THP-1, K562 and U937 was evaluated, and the cytotoxicity compared with the effects on non-cancerous mammalian cells, including peripheral blood mononuclear cells (PBMCs), HEK-293 and erythrocytes. ABP-CM4 reduced the number of viable cells of the leukemic cell lines after exposure for 24h. The reduction was concentration dependent, and the IC50 values ranged from 14 to 18 microM. Conversely, ABP-CM4, even at 120 microM, exhibited no cytotoxicity toward HEK-293 or PBMCs, indicating that there was no significant effect on these two types of non-cancer cells. ABP-CM4 at a concentration of 200 microM had no hemolytic activity on mammalian erythrocytes. Together, these results suggested a selective cytotoxicity in leukemia cells. Flow cytometry demonstrated that the binding activity of ABP-CM4 to leukemia cells was much higher than that to HEK-293 or PBMCs, and there was almost no binding to erythrocytes. FITC-labeled ABP-CM4 molecules were examined under a confocal microscope and found to be concentrated at the surface of leukemia cells and changes of the cell membrane were determined by a cell permeability assay, which led us to the conclusion that ABP-CM4 could act at the cell membrane for its anticancer activity on leukemia cells. Collectively, our results indicated that ABP-CM4 has the potential for development as a novel antileukemic agent.


Assuntos
Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Antineoplásicos/uso terapêutico , Proteínas de Insetos/uso terapêutico , Leucemia/tratamento farmacológico , Tensoativos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Proteínas de Insetos/síntese química , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Leucemia/metabolismo , Leucemia/patologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Modelos Moleculares , Peso Molecular , Estrutura Secundária de Proteína , Tensoativos/síntese química , Tensoativos/química , Tensoativos/metabolismo
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