STAT3 is involved in phosphatidic acid-induced Bcl-2 expression in HeLa cells

Phosphatidic acid (PA), the product of a PLD-mediated reaction, is a lipid second messenger that participates in various intracellular signaling events and is known to regulate a growing list of signaling proteins. We found that Bcl-2 was upregulated by PA treatment in HeLa cells. However, how PA upregulates Bcl-2 expression has not yet been studied. In this study, we tried to discover the mechanisms of Bcl-2 up-regulation by PA treatment in HeLa cells. Treatment with PA resulted in significantly increased expression of Bcl-2 in HeLa cells. Moreover, PA-induced Bcl-2 expression was blocked by mepacrine, an inhibitor of PLA2, but not by propranolol, an inhibitor of PA phospholyhydrolase (PAP). Treatment of 1,2-dipalmitoryl-sn-glycero-3-phosphate (DPPA) also increased Bcl-2 expression. These results indicate that Bcl-2 expression is mediated by lysophosphatidic acid (LPA), not by arachidonic acid (AA). Thereafter, we used MEK1/2 inhibitor, PD98059 to investigate the relationship between ERK1/2 MAPK and PA-induced Bcl-2 expression. PA-induced Bcl-2 expression was decreased when ERK1/2 was inhibited by PD98059. The transcription factor such as STAT3 which is controlled by ERK1/2 MAPK was increased along with Bcl-2 expression when the cells were treated with PA. Furthermore, STAT3 siRNA treatments inhibited PA-induced Bcl-2 expression, suggesting that STAT3 (Ser727) is involved in PA-induced Bcl-2 expression. Taken together, these findings indicate that PA acts as an important mediator for increasing Bcl-2 expression through STAT3 (Ser727) activation via the ERK1/2 MAPK pathway.

Opposing effects of quinacrine and chloroquine on the development of TA3 transplanted tumors in mice

Both quinacrine and chloroquine had been used as antimalarial agents. Furthermore, antineoplastic and antiviral effects have been described for quinacrine, while chloroquine has been described to induce viral replication and promote tumor growth. To search for differences in the growing rate of transplanted tumors, chloroquine or quinacrine were administered orally to AJ mice from 30 days previous to the inoculation of TA3 transplantable tumor cells, treatment being continued up to the end of the experiment. A control group, transplanted with tumor cells received tap drinking water. Marked differences between the three groups were found. Quinacrine had antitumoral effect, while chloroquine promoted a faster tumoral growth than controls. (p < 0.01). Results suggest caution in the use of chloroquine, because it might have a similar promoting effect on human neoplasia

Effects of mastoparan on a vascular contractility in rabbit aorta

Mastoparan is an amphiphilic tetradecapeptide derived from wasp venom which activates G-proteins. Several secondary effects have been attributed to this peptide, including activation of phospholipase and phosphatidylinositol kinase. The aim of the present study was to investigate the effects of mastoparan on vascular contractility. Rabbit aortic rings were cut and mounted on a force transducer to record isometric tension on a polygraph. The effects of mastoparan were then investigated on the contractile responses in the isolated rabbit aorta with or without endothelium. The results were summarized as follows; 1. Mastoparan caused biphasic response, a transient relaxation followed by a further contraction, in norepinephrine (NE)-precontracted ring with endothelium. These effects were not observed in the aorta in the absence of endothelium. 2. Mastoparan-induced transient relaxation was significantly inhibited by treatment with a N-omega-nitro-L-arginine or methylene blue. 3. When an inhibitor of phospholipase C, neomycin was added to the precontracted aortic ring with NE, the transient relaxation induced by mastoparan was inhibited, but sustained contraction was not inhibited. 4. When an inhibitor of phospholipase A2, quinacrine and inhibitor of the cyclooxygenase pathway, indomethacin, were added to a precontracted ring with NE, the transient relaxation induced by mastoparan was not inhibited, but sustained contraction was inhibited. 5. Mastoparan induced a contraction of the aorta either with or without endothelium. Indomethacin and nifedipine inhibited mastoparan-induced contraction. From the above results, we concluded that mastoparan acts on the endothelium and modifies the release of endothelium-derived relaxing factors such as nitric oxide and also endothelium-derived contracting factors such as metabolites of arachidonic acid.

Esterilizaçäo näo cirúrgica: caracterizaçäo das usuárias / Non-surgical female sterilization: characterization of the usuary

Análisou-se a utilizaçäo da quinacrina, como método de esterilizaçäo feminina näo-cirúrgica, definitivo e irreversível, em uma populaçäo de 506 mulheres, divididas pelo serviço em 3 grupos, inscritas na Seçäo de Anticonceptivos do Hospital Sotero del Rio, Santiago, Chile, no período de 1978 a 1986. A populaçäo foi estudada quanto as suas características bio-demográficas (idade, número de filhos vivos, estado civil, antecedentes de aborto induzido, métodos anticoncepcionais anteriormente utilizados, momento da vida reprodutiva por ocasiäo da esterilizaçäo. A eficácia mais alta deste método (1.9 por 100 mulheres/ano) foi apresentada pelo grupo de mulheres esterilizadas com 250 mg de quinacrina, em meses consecutivos. Os efeitos colaterais mais comuns foram amenorréia e algia pelviana pós-inserçäo. Säo apresentadas vantagens e desvantagens da utilizaçäo deste método para sua aplicaçäo a nível de política nacional de saúde

Esterelizaçäo näo-cirúrgica: caracterizaçäo das usuárias / Non-surgical female sterilization: users' characterization

O presente trabalho é uma análise da utilizaçäo da quinacrina, como método de esterilizaçäo feminina näo-cirúrgica, definitivo e irreversível, em uma populaçäo de 506 mulheres, divididas pelo serviço em 3 grupos, inscritas na Seçäo de Anticonceptivos do Hospital Sotero del Rio, Santiago, Chile, no período de 1978 a 1986. A populaçäo foi estudada quanto as suas características bio-demográficas (idade, número de filhos vivos, estado civil), antecendentes de aborto induzido, métodos anticoncepcionais anteriormente utilizados, momento da vida reprodutiva por ocasiäo da esterilizaçäo. A eficácia mais alta deste método (1.9 por 100 mulheres/ano) foi apresentada pelo grupo de mulheres esterelizadas com 250 mg. de quinacrina, em 2 meses consecutivos. Os efeitos colaterais mais comuns foram amenorréia e algia pelviana pos-inserçäo. Nas sugestöes säo apresentadas vantagens e desvantagens da utilizaçäo deste método para sua aplicaçäo a nível de política nacional de saúde .

Effect of glomerulo pressin on several isolated veins and arteries of different species

Se estudió el efecto de la glomerulopresina en varias venas aisladas de perro, conejo, hamster y rata y en arterias de perro. La glomerulopresina produjo contractión en las venas de perro: yugular, porta femoral, cava, ilíaca, esplénica y no tuvo efecto en las venas: pulmonar, mesentérica y renal. La glomerulopresina también produjo una contractión en algunas arterias de perro: ilíaca, femoral, renal y no tuvo efecto en la aorta, hepática, esplénica y pulmonar. En la rata aumentó la frecuencia del ritmo de las contracciones espontáneas de la vena porta. No se observó ningún efecto en las venas de conejo estudiadas: cava, yugular, ilíaca y porta. Tampoco tuvo efecto en la porta de hamster. En un grupo de experimentos se ensayó clorpromazina y mepacrina, in hibidores de la fosfolipasa A2. Estos inhibidores bloquearon la acción de la glomerulopresina en los tres vasos ensayados: yugular, porta y arteria ilíaca de perro. Estos resultados muestran que la glomerulopresina produce una contracción en varios, pero no en todos los vasos estudiados y sugieren que este efecto es mediado por la liberación de ácido araquidónico