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1.
Toxicol Lett ; 208(3): 214-24, 2012 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-22120587

RESUMO

Fluoranthene (Fla) is the most abundant polycyclic aromatic hydrocarbon (PAH) in diesel particulate extracts. Benzo[a]pyrene (BaP) is genotoxic and is a prototype of PAH carcinogens. Fla's toxicity and mutagenicity are minor relative to BaP's. Our data showed that Fla enhanced BaP-induced p53 expression and promoted BaP-induced cell death. In contrast, Fla decreased BaP-induced mutagenesis. Fla had almost no influence on the cell cycle. However, the effect of cotreatment with BaP (1µM) and Fla (10µM) in regulating the cell cycle was greater than that of BaP (2µM) alone. It is known that BaP activates the aryl hydrocarbon receptor (AhR), and, in turn, the AhR induces cytochrome P450 (Cyp)1a1 expression. The expression of Cyp1a1 corresponds well with the induction of apoptosis and mutagenesis by BaP. Fla did not activate the AhR or antagonize BaP's induction of AhR activity and Cyp1a1 expression. Therefore, the actions of Fla on BaP's toxicity were independent of the AhR signal and Cyp1a1. In summary, results indicated that Fla directs BaP-treated cells into death rather than mutagenesis, consequently preventing cells from being transformed. The novel cooperation between Fla and BaP provides valuable information for how to increase expression of the p53 tumor suppressor.


Assuntos
Benzo(a)pireno/toxicidade , Carcinógenos/toxicidade , Fluorenos/toxicidade , Proteína Supressora de Tumor p53/biossíntese , Animais , Western Blotting , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Interações Medicamentosas , Células Hep G2 , Humanos , Camundongos , Microscopia de Fluorescência , Testes de Mutagenicidade , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína Supressora de Tumor p53/genética
2.
Biomaterials ; 31(15): 4367-75, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20199810

RESUMO

Type I collagen constitutes a major portion of the extracellular matrix (ECM) in arterial wall and it is the major substrate for cell growth and differentiation. The goal of this study was to evaluate the differentiation and proliferation of placenta-derived multipotent cells (PDMCs) on polymerized type I collagen fibrils and monomer collagen. PDMCs grown on both polymerized collagen and monomer collagen with transforming growth factor (TGF)-beta treatment increases the expression of smooth muscle cell (SMC)-specific markers, including calponin, alpha-smooth muscle actin (alpha-SMA) and smooth muscle-myosin heavy chain (SM-MHC). Polymerized collagen increased the expressions of p21(CIP1) and p27(KIP1); decreased cyclin A, cyclin D1, cyclin-dependent protein kinase 2 (Cdk2); and led to G(0)/G(1) arrest in PDMCs. Furthermore, PDMC-differentiated SMCs exhibited significant collagen contractility in the presence or absence of endothelin-1 (ET-1) stimulation. By using specific inhibitors and small interfering RNA (siRNA), we demonstrated that p38 MAPK pathway and serum response factor (SRF)-DNA binding activity is critical for the polymerized collagen-induced PDMC differentiation into SMCs. Thus, polymerized collagen exhibits the great potential in inducing PDMCs differentiation into SMCs, and exerts anti-proliferative effect on PDMC-differentiated SMCs.


Assuntos
Técnicas de Cultura de Células , Diferenciação Celular/fisiologia , Proliferação de Células , Colágenos Fibrilares/metabolismo , Células-Tronco Multipotentes/fisiologia , Miócitos de Músculo Liso/fisiologia , Placenta/citologia , Animais , Becaplermina , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Feminino , Humanos , Proteínas dos Microfilamentos/metabolismo , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Fator de Crescimento Derivado de Plaquetas/farmacologia , Gravidez , Proteínas Proto-Oncogênicas c-sis , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fator de Resposta Sérica/genética , Fator de Resposta Sérica/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Calponinas
3.
Toxicol Lett ; 192(2): 252-60, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-19896525

RESUMO

1,10-phenanthroline (phen), flufenamic acid, and indomethacin are inhibitors of aldo-keto reductases 1C1 (AKR1C1), but only phen decreased the benzo[a]pyrene (BaP)-induced cytochrome P450 1a1 (Cyp1a1) protein level. Therefore the decrease in the BaP-induced Cyp1a1 protein level was not due to inhibition of Akr1c1, but to phen itself. Phen decreased the BaP-induced Cyp1a1 promoter activity and protein expression, and in contrast, it increased Cyp1a1 mRNA, resulting from an increase in mRNA stability. Phen is also known as a transition metal ion-chelator. Along with the phen study, we also found that Zn(2+), Fe(2+) and Cu(2+) increased Cyp1a1 mRNA and protein stability. Our results show that phen stabilized the mRNA of Cyp1a1, although it decreased cell viability. In addition, Zn(2+) and Fe(2+) highly neutralized phen's suppression of Cyp1a1 protein expression, but they only slightly neutralized phen's promotion of mRNA stability and suppression of cell viability, and had no effect on phen's suppression of promoter activity. Phen's effect on Cyp1a1 expression was reversible, which indicates that phen is non-covalently linked to its target. This report elucidates a new role for phen of stabilizing Cyp1a1 mRNA, and provides information for further studies on mRNA stabilization.


Assuntos
Citocromo P-450 CYP1A1/genética , Fenantrolinas/farmacologia , Estabilidade de RNA/efeitos dos fármacos , RNA Mensageiro/metabolismo , Xenobióticos/farmacologia , Benzo(a)pireno/farmacologia , Cátions Bivalentes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cobre/farmacologia , Citocromo P-450 CYP1A1/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Ferro/farmacologia , Transcrição Gênica/efeitos dos fármacos , Zinco/farmacologia
4.
Int Urogynecol J Pelvic Floor Dysfunct ; 20(6): 689-93, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19165412

RESUMO

INTRODUCTION: The aim of this study is to determine the efficacy of preoperative ureteral catheterization as a prophylactic measure to prevent ureteral injury and related complications. METHODS: All major gynecologic operations performed between January 1996 and December 2007 were included and prospectively randomized into with and without catheterization groups. The medical records allowed the identification of all urinary tract complications and ureteral injuries. RESULTS: Bilateral prophylactic ureteral catheterization was performed in 1,583 patients. A ureteral injury occurred in 19 (1.20%) out of 1,583 patients. Seventeen ureteral injuries (1.09%) occurred out of 1,558 patients without prophylactic ureteral catheterization. There was no statistically significant difference in the incidence of ureteral injury between the different interventional groups (p = 0.774). CONCLUSION: The use of prophylactic ureteral catheters did not eliminate ureteral injuries in our patients. The presence of ureteral catheters should not supplant meticulous surgical techniques and direct visualization of the ureters during gynecologic surgery.


Assuntos
Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Doença Iatrogênica/prevenção & controle , Ureter/lesões , Doenças Ureterais/etiologia , Cateterismo Urinário , Adulto , Feminino , Hospitais Comunitários , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Doenças Ureterais/prevenção & controle
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