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      Explanted Glomeruli: Utility and Limitations

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          Ex vivo incubation of isolated glomeruli has been used for many years to investigate biochemical properties of glomeruli. However, little has been understood about whether and how isolation and explanation per se affect the structure and function of the glomerulus. We recently reported that ex vivo incubation of isolated normal glomeruli results in severe apoptosis of podocytes, activation of the family of mitogen-activated protein kinase and expression of several genes regulated by activator protein 1. In this article, we summarize our current findings and discuss the utility and limitations of explanted glomeruli.

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          Mechanical stretch induces hypertrophic responses in cardiac myocytes of angiotensin II type 1a receptor knockout mice.

          Many lines of evidence have suggested that angiotensin II (AngII) plays an important role in the development of cardiac hypertrophy through AngII type 1 receptor (AT1). To determine whether AngII is indispensable for the development of mechanical stress-induced cardiac hypertrophy, we examined the activity of mitogen-activated protein kinase (MAPK) family and the expression of the c-fos gene as hypertrophic responses after stretching cultured cardiac myocytes of AT1a knockout (KO) mice. When cardiac myocytes were stretched by 20% for 10 min, extracellular signal-regulated protein kinases (ERKs) were strongly activated in KO cardiomyocytes as well as wild type (WT) myocytes. Both basal and stimulated levels of ERKs were higher in cardiomyocytes of KO mice than in those of WT mice. Activation of another member of the MAPK family, p38(MAPK), and expression of the c-fos gene were also induced by stretching cardiac myocytes of both types of mice. An AT1 antagonist attenuated stretch-induced activation of ERKs in WT cardiomyocytes but not in KO cardiomyocytes. Down-regulation of protein kinase C inhibited stretch-induced ERK activation in WT cardiomyocytes, whereas a broad spectrum tyrosine kinase inhibitor (genistein) and selective inhibitors of epidermal growth factor receptor (tyrphostin, AG1478, and B42) suppressed stretch-induced activation of ERKs in KO cardiac myocytes. Epidermal growth factor receptor was phosphorylated at tyrosine residues by stretching cardiac myocytes of KO mice. These results suggest that mechanical stretch could evoke hypertrophic responses in cardiac myocytes that lack the AT1 signaling pathway possibly through tyrosine kinase activation.
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            Spontaneous apoptosis of podocytes in explanted glomeruli: Technical Note


              Author and article information

              Nephron Exp Nephrol
              Cardiorenal Medicine
              S. Karger AG
              31 August 2001
              : 9
              : 5
              : 349-354
              Department of Medicine, Royal Free and University College Medical School, University College London, Jules Thorn Institute, Middlesex Hospital, London, UK
              52631 Exp Nephrol 2001;9:349–354
              © 2001 S. Karger AG, Basel

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              Figures: 3, References: 32, Pages: 6
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              Technical Seminar


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