RESUMEN
Peroxisomes are essential in cellular metabolism as their dysgenesis or defects in single enzymes or impairment of multiple peroxisomal enzymatic functions have been found in several inherited metabolic diseases with serious clinical sequelae. The assembly and formation of these cytoplasmic organelles constitute a major and intriguing research topic. In the present study the biogenesis of peroxisomes and the developmental patterns of their enzymes have been reviewed during embryonic and/or post-embryonic ontogenesis of lower (amphibians) and higher (avians, mammals) vertebrates. In developing vertebrates, epithelial cell differentiation is accompanied by increases in frequency and size of peroxisomes. The tissue-specific expression of peroxisomal enzymes contributes substantially to the biochemical maturation of epithelial cells. The relationship between biogenesis of peroxisomes, expression of peroxisomal enzymes and structural and functional cellular phenotype has also been investigated in differentiating epithelial cells along the crypt-villus axis of the adult rat intestine. Cytochemical studies at the ultrastructural level have provided evidence that peroxisomes are already present in proliferating cells of the intestinal crypt region before they begin to differentiate. Migration and differentiation of intestinal epithelial cells from crypt to villus compartments are marked by significant increases in number and size of catalase-positive structures. Increasing activity gradients from crypt to surface areas are found for the peroxisomal oxidases examined (enzymes of the peroxisomal beta-oxidation system, D-amino acid oxidase and polyamine oxidase). Thus, peroxisomes are more and more involved in oxidative metabolic pathways as intestinal epithelial cells differentiate. Finally, we have analyzed the peroxisomal behaviour in human neoplastic epithelial cells. The presence of peroxisomes has been cytochemically revealed in human breast and colon carcinomas. Peroxisomal enzyme specific activities are significantly lower in human breast and colon carcinomas than in the adjacent healthy mucosa. Furthermore, a relationship is found between the specific activities of some peroxisomal enzymes and the histological tumour grades.
Asunto(s)
Microcuerpos/fisiología , Neoplasias/ultraestructura , Anfibios/crecimiento & desarrollo , Animales , Diferenciación Celular/fisiología , Humanos , Intestinos/ultraestructura , Metamorfosis Biológica/fisiología , Microcuerpos/metabolismo , Vertebrados/embriología , Vertebrados/crecimiento & desarrolloRESUMEN
The presence of peroxisomes and their enzymatic content were investigated and compared in healthy and neoplastic human breast epithelial cells using cytochemical studies at the ultrastructural level as well as Western blot and biochemical analyses. Ultrastructural cytochemistry revealed the presence of these organelles in both normal and neoplastic breast tissues. Their mean diameter was 0.27 +/- 0.11 micron. No significant difference was noted between numbers of peroxisomes in normal and neoplastic breast epithelia. Catalase, D-amino acid oxidase, and urate oxidase were found to be expressed in mammary carcinoma and in surrounding non-malignant tissue when the postnuclear supernatant fractions prepared from homogenates were assessed by Western blot techniques. Their specific activities and that of fatty acyl CoA oxidase as determined spectrophotometrically were found to be diminished in the tumour when compared with the control tissue. On the other hand, no significant difference was found in the specific activity of the L-alpha-hydroxy acid oxidase of normal and neoplastic human breast tissues. Investigations of the relationship between peroxisomal enzymes and tumour grade revealed that catalase, urate oxidase, and fatty acyl CoA oxidase activities in breast neoplastic tissues belonging to grade III were significantly lower than in the adjacent normal tissues.
Asunto(s)
Neoplasias de la Mama/enzimología , Mama/enzimología , Microcuerpos/enzimología , Adulto , Anciano , Anciano de 80 o más Años , Western Blotting , Mama/ultraestructura , Neoplasias de la Mama/ultraestructura , Femenino , Humanos , Microcuerpos/ultraestructura , Persona de Mediana EdadRESUMEN
Global cerebral ischemia (four vessel model) was induced in renovascular hypertensive rats (two kidney, one clip model) chronically treated with intraperitoneal administration of angiotensin I converting enzyme inhibitors, either captopril (100 mg/kg per day) or Wy-44,655 (10 mg/kg per day). Mortality following cerebral ischemia was higher in renovascular hypertensive rats than in normotensive controls. Reduction of blood pressure with captopril or Wy-44,655, lowered mortality. In surviving renovascular hypertensive and normotensive rats cerebral ischemia induced hyperactivity and lesions of the CA1 area of the hippocampus. Prolonged treatment with captopril--but not with Wy-44,655--reduced hyperactivity and the extent of the CA1 lesions. In conclusion, hypertension increases mortality following cerebral ischemia but does not affect the extent of brain injury in survivors. Prior treatment with converting enzyme inhibitors lowers mortality. Treatment with captopril attenuates brain injury in survivors.