Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Acta Pharmacol Sin ; 29(9): 1006-12, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18718168

RESUMO

AIM: To study the effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis, such as wuweizisu C, gomisin N, gomisin A, and schisandrin, on the membrane potential in C6 glioma cells. METHODS: The membrane potential was estimated by measuring the fluorescence change in DiBAC-loaded glioma cells. RESULTS: Wuweizisu C decreased the membrane potential in a concentration-dependent manner. Gomisin N and gomisin A, however, showed differential modulation and no change was induced by schisandrin or dimethyl- 4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate, a synthetic drug derived from dibenzocyclooctadiene lignans. We found no involvement of G(i/o ) proteins, phospholipase C, and extracellular Na(+) on the wuweizisu C-induced decrease of the membrane potential. Wuweizisu C by itself did not change the intracellular Ca(2+)[Ca(2+)](i) concentration, but decreased the ATP-induced Ca(2+) increase in C6 glioma cells. The 4 lignans at all concentrations used in this study did not induce any effect on cell viability. Furthermore, we found a similar decrease of the membrane potential by wuweizisu C in PC12 neuronal cells. CONCLUSION: Our results suggest that the decrease in the membrane potential and the modulation of [Ca(2+)](i) concentration by wuweizisu C could be important action mechanisms of wuweizisu C.


Assuntos
Lignanas/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Compostos Policíclicos/farmacologia , Schisandra/química , Animais , Cálcio/metabolismo , Linhagem Celular Tumoral , Ciclo-Octanos/farmacologia , Frutas/química , Proteínas de Ligação ao GTP/metabolismo , Glioma/fisiopatologia , Humanos , Indicadores e Reagentes , Células PC12 , Ratos , Fosfolipases Tipo C/metabolismo
2.
Arch Pharm Res ; 31(3): 310-7, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18409043

RESUMO

Lysophosphatidylserine (LPS) can be generated following phosphatidylserine-specific phospholipase A2 activation. The effects of LPS on cellular activities and the identities of its target molecules, however, have not been fully elucidated. In this study, we observed that LPS stimulated intracellular calcium increased in mouse bone marrow-derived mast cells (BMMC), and rat C6 glioma and human HCT116 colon cancer cells and compared the LPS-induced Ca2+ increases with the response by lysophosphatidic acid (LPA), a structurally related bioactive lysolipid. In order to test involvement of signaling molecules in the LPS-induced Ca2+ signaling, we used pertussis toxin (PTX), U73122, and 2-APB, which are specific inhibitors for G proteins, phospholipase C (PLC), and IP3 receptors, respectively. The increases due to LPS and LPA were inhibited by PTX, U-73122 and 2-APB, suggesting that both lipids stimulate calcium signaling via G proteins (Gi/o types), PLC activation, and subsequent IP3 production, although the sensitivity to pharmacological inhibitors varied from complete inhibition to partial inhibition depending on cell type and lysolipid. Furthermore, we observed that Ki16425 completely inhibited an LPS-induced Ca2+ response in three cell types, but that the effect of VPC32183 varied from complete inhibition in BMMC and C6 glioma cells to partial inhibition in HCT116 cells. Therefore, we conclude that LPS increases [Ca2+]i through Ki16425/VPC32183-sensitive G protein-coupled receptors (GPCR), G protein, PLC, and IP3 in mouse BMMC, rat C6, and human HCT116 cells.


Assuntos
Células da Medula Óssea/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Glioma/metabolismo , Isoxazóis/farmacologia , Lisofosfolipídeos/metabolismo , Mastócitos/efeitos dos fármacos , Organofosfatos/farmacologia , Propionatos/farmacologia , Piridinas/farmacologia , Receptores de Ácidos Lisofosfatídicos/antagonistas & inibidores , Animais , Células da Medula Óssea/enzimologia , Células da Medula Óssea/metabolismo , Neoplasias do Colo/enzimologia , Neoplasias do Colo/patologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Estrenos/farmacologia , Glioma/enzimologia , Glioma/patologia , Células HCT116 , Humanos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Mastócitos/enzimologia , Mastócitos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Toxina Pertussis/farmacologia , Pirrolidinonas/farmacologia , Ratos , Receptores de Ácidos Lisofosfatídicos/metabolismo , Fatores de Tempo , Fosfolipases Tipo C/antagonistas & inibidores , Fosfolipases Tipo C/metabolismo
3.
Prostaglandins Other Lipid Mediat ; 84(3-4): 174-83, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17991619

RESUMO

We investigated the effects of serum on lysophospholipid-induced cytotoxicity in Jurkat T cells. We found that sphingosylphosphorylcholine (SPC, also known as lysosphingomyelin) induced cytotoxicity and that albumin in serum could protect cells by binding directly to SPC. Furthermore, we also found that SPC induced ROS generation, increased [Ca(2+)](i), and decreased MMP. However, those effects were only observed at concentrations higher than 10 microM and were only induced in albumin-free media. Therefore, SPC may be trapped by albumin in plasma and unable to exert its effects under normal conditions, although at high concentrations, SPC could induce several responses such as ROS generation, increased [Ca(2+)](i), and decreased MMP in Jurkat T cells.


Assuntos
Fosforilcolina/análogos & derivados , Soroalbumina Bovina/metabolismo , Soroalbumina Bovina/farmacologia , Esfingosina/análogos & derivados , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Animais , Cálcio/metabolismo , Calorimetria , Bovinos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células Jurkat , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fosforilcolina/antagonistas & inibidores , Fosforilcolina/metabolismo , Fosforilcolina/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Esfingosina/antagonistas & inibidores , Esfingosina/metabolismo , Esfingosina/toxicidade , Linfócitos T/metabolismo
4.
Arch Pharm Res ; 30(9): 1096-101, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17958326

RESUMO

Previously, we reported on the distinct effects of bioactive lysophospholipids, including lysophosphatidic acid (LPA), lysophosphatidylcholine (LPC), and sphingosylphosphorylcholine (SPC), on membrane potentials in rat C6 glioma cells. In the present report we have tested lysophosphatidylserine (LPS), another bioactive lysophospholipid, on membrane potentials in the same cell line. Membrane potentials were estimated by measuring the fluorescence changes of DiBAC-loaded glioma cells. LPS largely increased membrane potentials in a concentration-dependent manner. The LPS-induced membrane potential increases were not affected by treatment with pertussis toxin, implying no involvement of Gi/o proteins. In contrast to other lysophospholipids, the LPS-induced membrane potential increase was not diminished by a Na(+)-free media but was enhanced by suramin. Furthermore, this change was blunted by EIPA, an inhibitor of Na(+)/H(+) exchanger, but not by SITS, a specific inhibitor of bicarbonate transporter. Our observations suggest that LPS acts on membrane potentials in a unique manner in the C6 glioma cells, although the precise action mechanism requires additional investigation.


Assuntos
Glioma/fisiopatologia , Lisofosfolipídeos/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Ácido 4-Acetamido-4'-isotiocianatostilbeno-2,2'-dissulfônico/farmacologia , Amilorida/análogos & derivados , Amilorida/farmacologia , Animais , Linhagem Celular Tumoral , Proteínas de Ligação ao GTP/fisiologia , Glioma/patologia , Ratos , Receptores Acoplados a Proteínas G/fisiologia
5.
J Pharm Pharmacol ; 59(7): 1035-41, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17637200

RESUMO

Treatment with isoprenaline led to a change in the cell morphology of rat C6 glioma cells. This morphological change was reverted by the addition of sphingosine 1-phosphate (S1P). Using this morphological change as a response marker we determined that DS-SG-44 ((2S,3R)-2-amino-3-hydroxy-4-(4-octylphenyl)butyl phosphoric acid) was an agonist of S1P receptors. The DS-SG-44-induced morphological reversion was not observed with such structurally related molecules as DS-SG-45 ((2S,3R)-2-amino-3-hydroxy-4-(3-octylphenyl)butyl phosphoric acid) and DS-SG-12 ((2S,3R)-2-amino-4-(4-octylphenyl)butane-1,3-diol). The S1P- and DS-SG-44-induced shape changes were neither reproduced with the S1P1/S1P3 receptor agonist VPC24191 nor inhibited by the S1P1/S1P3 receptor antagonist, VPC23019. Transfection with small interfering RNA (siRNA) for the S1P2 receptor greatly inhibited the DS-SG-44-induced shape change, and in part an S1P-induced response. In the presence of VPC23019, siRNA transfection for the S1P2 receptor almost completely blocked the S1P- and DS-SG-44-induced shape changes. Our results suggested that DS-SG-44, a newly-synthesized S1P analogue, acted as an S1P receptor agonist and that the S1P-induced shape change in rat C6 glioma cells was mediated mainly through the S1P2 receptor, and cooperatively through the S1P1/S1P3 receptors.


Assuntos
Forma Celular/efeitos dos fármacos , Lisofosfolipídeos/síntese química , Ácidos Fosfóricos/síntese química , Receptores de Lisoesfingolipídeo/agonistas , Esfingosina/análogos & derivados , Análise de Variância , Animais , Glioma , Lisofosfolipídeos/química , Lisofosfolipídeos/farmacologia , Ácidos Fosfóricos/química , Ácidos Fosfóricos/farmacologia , Ratos , Receptores de Lisoesfingolipídeo/genética , Esfingosina/síntese química , Esfingosina/química , Esfingosina/farmacologia , Células Tumorais Cultivadas
6.
Prostaglandins Other Lipid Mediat ; 83(4): 268-76, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17499746

RESUMO

Phosphatidic acid (PA) increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in C6 rat glioma and L2071 mouse fibroblast cells. Dioleoyl PA (PA, 18:1) was the most efficacious, followed by dipalmitoyl PA (16:0 PA) and dimyristoyl PA (14:0 PA). Lysophosphatidic acid (LPA) also increased the [Ca(2+)](i) in the both cells. PA desensitized LPA-induced Ca(2+) response completely in C6 cells, but partly in L2071 cells. Treatment of pertussis toxin (PTX), a specific inhibitor of G(i/o)-type G proteins, completely ameliorated LPA- and PA-induced Ca(2+) response in C6 cells. However, in L2071 cells, PTX inhibited PA-induced Ca(2+) increase by 80% and LPA-induced one by 20%. Ki16425, a specific inhibitor of LPA(1)/LPA(3) receptors, completely inhibited both LPA- and PA-induced Ca(2+) responses in C6 cells. On the other hand, in L2071 cells, Ki16425 completely inhibited PA-induced Ca(2+) response, but partly LPA-induced one. VPC32183, another specific inhibitor of LPA(1)/LPA(3) receptors, completely inhibited LPA- and PA-induced Ca(2+) responses in both C6 and L2071 cells. Therefore, PA and LPA appear to increase [Ca(2+)](i) through Ki16425/VPC32183-sensitive LPA receptor coupled to PTX-sensitive G proteins in C6 cells. In L2071 cells, however, LPA increases [Ca(2+)](i) through Ki16425-insensitive LPA receptor coupled to PTX-insensitive G proteins and Ki16425-sensitive LPA receptor coupled to PTX-sensitive G protein, whereas PA utilized only the latter pathway. Our results suggest that PA acts as a partial agonist on endogenous LPA receptors, which are sensitive to Ki16425 and coupled to PTX-sensitive G protein, but not on LPA receptors, which are not sensitive to Ki16425 and coupled to PTX-insensitive G protein.


Assuntos
Cálcio/metabolismo , Fibroblastos/efeitos dos fármacos , Ácidos Fosfatídicos/farmacologia , Receptores de Ácidos Lisofosfatídicos/metabolismo , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Fibroblastos/citologia , Fibroblastos/metabolismo , Expressão Gênica/efeitos dos fármacos , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Isoxazóis/farmacologia , Lisofosfolipídeos/farmacologia , Camundongos , Toxina Pertussis/farmacologia , Ácidos Fosfatídicos/química , Propionatos/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Receptores de Ácidos Lisofosfatídicos/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo
7.
Environ Toxicol Chem ; 22(2): 302-12, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12558161

RESUMO

Dodecylbenzene sulfonate (DBS) is a component of linear alkylbenzene sulfonate (LAS), an anionic surfactant, mainly used in household detergents. Due to the large quantity of DBS in use, there is concern over adverse environmental effects. This work examined the toxicokinetics and toxicity of the 2-phenyl isomer of dodecylbenzene sulfonate in 4-d, 10-d, and partial life-cycle tests on the midge, Chironomus riparius, exposed to aqueous solutions. Toxicokinetics were determined in 10-d uptake and 5-d elimination tests. The toxicokinetics were based on parent compound concentration in water and yielded an uptake coefficient (ku) of 17.5 (14.87-20.20) ml/g/h, an elimination rate constant (ke) of 0.073 (0.062-0.085) per h, a bioconcentration factor (BCF) of 56 to 240, and a half-life (t 1/2) of 9.5 (8.0-11.0) h. Biotransformation measurements did not reveal evidence for DBS metabolism. Thus, body residues, determined in the toxicity study, represent parent compound. In toxicity tests, 4- and 10-d LR50s (the body residue required to cause 50% mortality) in live midges were 0.72 (0.65-0.79) and 0.18 (0.08-0.42) mmol/kg, respectively. Thirty-day LR50s were 0.18 (0.09-1.64) and 0.21 (0.15-0.39) mmol/kg in duplicate studies. Of the sublethal endpoints, only developmental time increase was significant, with the lowest-observed-effect residues of 0.085 (0.067-0.105) and 0.100 (0.087-0.114) mmol/kg for male and female midges, respectively. Deformities in surviving larvae were also observed as chronic responses for body residues exceeding the 30-d LR50. The body residues required for mortality suggest that DBS acts like a polar narcotic in the midge.


Assuntos
Benzenossulfonatos/toxicidade , Chironomidae/efeitos dos fármacos , Tensoativos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Benzenossulfonatos/farmacocinética , Carga Corporal (Radioterapia) , Peso Corporal/efeitos dos fármacos , Chironomidae/metabolismo , Feminino , Fertilidade/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/metabolismo , Dose Letal Mediana , Masculino , Tensoativos/farmacocinética , Fatores de Tempo , Poluentes Químicos da Água/farmacocinética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...