Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
1.
Clinics ; 68(8): 1079-1083, 2013. tab, graf
Artículo en Inglés | LILACS | ID: lil-685434

RESUMEN

OBJECTIVES: Noonan and Noonan-related syndromes are common autosomal dominant disorders with neuro-cardio-facial-cutaneous and developmental involvement. The objective of this article is to describe the most relevant tegumentary findings in a cohort of 41 patients with Noonan or Noonan-related syndromes and to detail certain aspects of the molecular mechanisms underlying ectodermal involvement. METHODS: A standard questionnaire was administered. A focused physical examination and a systematic review of clinical records was performed on all patients to verify the presence of tegumentary alterations. The molecular analysis of this cohort included sequencing of the following genes in all patients: PTPN1, SOS1, RAF1, KRAS, SHOC2 and BRAF. RESULTS: The most frequent tegumentary alterations were xeroderma (46%), photosensitivity (29%), excessive hair loss (24%), recurrent oral ulcers (22%), curly hair (20%), nevi (17%), markedly increased palmar and plantar creases (12%), follicular hyperkeratosis (12%), palmoplantar hyperkeratosis (10%), café-au-lait spots (10%) and sparse eyebrows (7%). Patients with mutations in PTPN11 had lower frequencies of palmar and plantar creases and palmar/plantar hyperkeratosis compared with the other patients. CONCLUSIONS: We observed that patients with mutations in genes directly involved in cell proliferation kinase cascades (SOS1, BRAF, KRAS and RAF1) had a higher frequency of hyperkeratotic lesions compared with patients with mutations in genes that have a more complex interaction with and modulation of cell proliferation kinase cascades (PTPN11). .


Asunto(s)
Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Síndrome de Noonan/patología , Enfermedades de la Piel/patología , Piel/patología , Quinasas MAP Reguladas por Señal Extracelular/genética , Mutación , Síndrome de Noonan/genética , Estudios Prospectivos , /genética , Factores Sexuales , Encuestas y Cuestionarios , Enfermedades de la Piel/genética
2.
Experimental & Molecular Medicine ; : 259-268, 2009.
Artículo en Inglés | WPRIM | ID: wpr-49341

RESUMEN

Matrix metalloproteinase-9 (MMP-9) secreted from macrophages plays an important role in tissue destruction and inflammation through degradation of matrix proteins and proteolytic activation of cytokines/chemokines. Whereas the MEK-ERK and PI3K-Akt pathways up-regulate MMP-9 expression, regulation of MMP-9 by JNK remains controversial. Presently, we aimed to determine the role of JNK in MMP-9 regulation in Raw 264.7 cells. Inhibition of JNK by the JNK inhibitor SP600125 induced MMP-9 in the absence of serum and suppressed the expression of TNF-alpha, IL-6 and cyclooxygenase-2 in LPS-treated Raw 264.7 cells. In a knockdown experiment with small interfering RNA, suppression of JNK1 induced MMP-9 expression. Interestingly, mouse serum suppressed SP600125-mediated MMP-9 induction, similar to IFN-gamma. However, the inhibitory activity of mouse serum was not affected by pyridone 6, which inhibits Janus kinase downstream to IFN-gamma. In addition to mouse serum, conditioned media of Raw 264.7 cells contained the inhibitory factor(s) larger than 10 kDa, which suppressed SP600125- or LPS-induced MMP-9 expression. Taken together, these data suggest that JNK1 suppresses MMP-9 expression in the absence of serum. In addition, the inhibitory factor(s) present in serum or secreted from macrophages may negatively control MMP-9 expression.


Asunto(s)
Animales , Ratones , Antracenos/metabolismo , Línea Celular , Medios de Cultivo Condicionados/química , Activación Enzimática , Inducción Enzimática , Inhibidores Enzimáticos/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/genética , Regulación Enzimológica de la Expresión Génica , Sistema de Señalización de MAP Quinasas/fisiología , Macrófagos/citología , Metaloproteinasa 9 de la Matriz/genética , Proteína Quinasa 8 Activada por Mitógenos/genética , FN-kappa B/genética , Proteínas Proto-Oncogénicas c-akt/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/genética
3.
Experimental & Molecular Medicine ; : 677-685, 2006.
Artículo en Inglés | WPRIM | ID: wpr-106417

RESUMEN

The early growth response-1 gene (egr-1) encodes a zinc-finger transcription factor Egr-1 and is rapidly inducible by a variety of extracellular stimuli. Anisomycin (ANX), a protein synthesis inhibitor, stimulates mitogen-activated protein kinase (MAPK) pathways and thereby causes a rapid induction of immediate-early response genes. We found that anisomycin treatment of U87MG glioma cells resulted in a marked, time-dependent increase in levels of Egr-1 protein. The results of Northern blot analysis and reporter gene assay of egr-1 gene promoter (Pegr-1) activity indicate that the ANX- induced increase in Egr-1 occurs at the transcriptional level. Deletion of the serum response element (SRE) in the 5'-flanking region of egr-1 gene abolished ANX-induced Pegr-1 activity. ANX induced the phosphorylation of the ERK1/2, JNK, and p38 MAPKs in a time-dependent manner and also induced transactivation of Gal4-Elk-1, suggesting that Elk-1 is involved in SRE-mediated egr-1 transcription. Transient transfection of dominant-negative constructs of MAPK pathways blocked ANX-induced Pegr-1 activity. Furthermore, pretreatment with specific MAPK pathway inhibitors, including the MEK inhibitor U0126, the JNK inhibitor SP600125, and the p38 kinase inhibitor SB202190, completely inhibited ANX-inducible expression of Egr-1. Taken together, these results suggest that all three MAPK pathways play a crucial role in ANX-induced transcriptional activation of Pegr-1 through SRE-mediated transactivation of Elk


Asunto(s)
Humanos , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteína Elk-1 con Dominio ets/genética , Activación Transcripcional/efectos de los fármacos , Elemento de Respuesta al Suero , Inhibidores de Proteínas Quinasas/farmacología , Biosíntesis de Proteínas/efectos de los fármacos , Regiones Promotoras Genéticas/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Quinasas MAP Reguladas por Señal Extracelular/genética , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Línea Celular Tumoral , Anisomicina/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA