RESUMEN
Excessive physical exercise may lead to disturbance of the entire homeostasis in the body, including damage not only in skeletal muscles but also in many distant organs. The mechanisms responsible for the exercise-induced changes could include oxidative stress or angiotensin II. We previously showed that acute exercise led to apoptosis in kidney but not as a result of oxidative stress. In this study, we examined the role of angiotensin II and its AT1 and AT2 receptors in mediation of exercise-induced apoptosis in kidney. We clearly demonstrated that acute physical exercise induced apoptosis in renal cells of distal convoluted tubuli and cortical and medullary collecting ducts. Moreover, the cells displayed an increased expression of both AT1 and AT2 angiotensin II receptors and of p53 protein. The results suggest that angiotensin II could upregulate p53 expression in renal distal convoluted tubular cells and in the cells collecting ducts via both AT1 and AT2 receptors, which might be the crucial apoptosis-mediating mechanism in kidneys after excessive exercise.
Asunto(s)
Apoptosis/fisiología , Riñón/citología , Condicionamiento Físico Animal/fisiología , Receptor de Angiotensina Tipo 1/fisiología , Receptor de Angiotensina Tipo 2/fisiología , Angiotensina II/fisiología , Animales , Regulación de la Expresión Génica/fisiología , Inmunohistoquímica , Riñón/química , Riñón/fisiología , Túbulos Renales Colectores/química , Túbulos Renales Colectores/citología , Túbulos Renales Colectores/fisiología , Túbulos Renales Distales/química , Túbulos Renales Distales/citología , Túbulos Renales Distales/fisiología , Masculino , Estrés Oxidativo/fisiología , Ratas , Ratas Wistar , Receptor de Angiotensina Tipo 1/análisis , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 2/análisis , Receptor de Angiotensina Tipo 2/genética , Proteína p53 Supresora de Tumor/análisis , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/fisiologíaRESUMEN
Intensive physical exercise disturbs the entire homeostasis in the body and leads to changes in haemodynamic and metabolic alterations not only in skeletal muscles but also in many distant organs. In response to acute physical exercise, a decrease of the glomerular filtration may occur, followed by stimulation of the renin-angiotensin system (RAS). Recent studies have shown that both AT1 and AT2 angiotensin receptors may play a role in mediating the apoptotic process in the kidney. Our previous studies have demonstrated an occurrence of apoptosis in rat renal tubular cells after an excessive exercise. The aim of the present study was to determine the possible mechanism of exercise-induced apoptosis in rat kidney. The analysis was performed on kidneys of rats, subjected to treadmill running until exhaustion. Apoptosis was detected in paraffin sections by the TUNEL technique. The expression of AT1 and AT2 receptors in renal tubular cells was examined by immunohistochemistry and Western blot. Our results confirmed that apoptosis after physical exercise is present in renal distal tubular cells. Moreover, there was an increased expression of AT1 and AT2 receptors in distal tubular cells. These studies suggest that physical exercise may induce apoptosis by a mechanism, involving the activation of angiotensin AT1 and AT2 receptors.
Asunto(s)
Apoptosis/fisiología , Corteza Renal/fisiología , Túbulos Renales/fisiología , Condicionamiento Físico Animal , Receptor de Angiotensina Tipo 1/metabolismo , Receptor de Angiotensina Tipo 2/metabolismo , Animales , Corteza Renal/citología , Túbulos Renales/citología , Masculino , Modelos Animales , Ratas , Ratas WistarRESUMEN
Bacteriophages (phages) as bacterial viruses are generally believed to have no intrinsic tropism for mammalian cells. In this study the interactions between phages and various eukaryotic cells were investigated. Binding of phages to the membranes of cancer and normal blood cells was observed. Moreover, it was shown that the wild-type phage T4 (wtT4) and its substrain HAP1 with enhanced affinity for melanoma cells inhibit markedly and significantly experimental lung metastasis of murine B16 melanoma cells by 47% and 80%, respectively. A possible molecular mechanism of these effects, namely a specific interaction between the Lys-Gly-Asp motif of the phage protein 24 and beta3-integrin receptors on target cells is proposed. It was also shown that anti-beta3 antibodies and synthetic peptides mimicking natural beta3 ligands inhibit the phage binding to cancer cells. This is in line with the well-described beta3 integrin-dependent mechanism of tumor metastasis. It is concluded that the blocking of beta3 integrins by phage preparations results in a significant decrease in tumor invasiveness.