Up-Regulation of the Human Serum and Glucocorticoid-Dependent Kinase 1 in Glomerulonephritis

Abstract Glomerulonephritis is paralleled by excessive formation of transforming growth factor-beta (TGF-ß), which participates in the pathophysiology of the disease. Recently, a novel downstream target of TGF-ß has been identified, i.e. the human serum and glucocorticoid-dependent kinase 1 (hSGK1), a serine/threonine kinase participating in the regulation of Na + transport. The present study was performed to elucidate transcriptional regulation of hSGK1 in glomerulonephritis. To this end, in situ hybridization was performed in biopsies from patients with clinical diagnosis of glomerulonephritis. hSGK1 transcript levels were moderately enhanced in 5 out of 9 patients and strongly enhanced in 4 out of 9 patients. Distal nephron epithelial cell hSGK1 transcript levels were low or absent in 7 of the 9 patients but markedly enhanced in 2 of the 9 patients. In conclusion, glomerulonephritis leads to glomerular and in some cases to epithelial up-regulation of hSGK1 transcription

Plasma Corticosterone Activates SGK1 and Induces Morphological Changes in Oligodendrocytes in Corpus Callosum

Repeated stressful events are known to be associated with onset of depression. Further, stress activates the hypothalamic–pituitary–adrenocortical (HPA) system by elevating plasma cortisol levels. However, little is known about the related downstream molecular pathway. In this study, by using repeated water-immersion and restraint stress (WIRS) as a stressor for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to WIRS activates the 3-phosphoinositide-dependent protein kinase (PDK1)–serum glucocorticoid regulated kinase (SGK1)–N-myc downstream-regulated gene 1 (NDRG1)–adhesion molecule (i.e., N-cadherin, α-catenin, and β-catenin) stabilization pathway via an increase in plasma corticosterone levels; (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes; and (3) after recovery from chronic stress, the abnormal arborization of oligodendrocytes and depression-like symptoms return to the control levels. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms

Telemedizinische Erfassung der Prävalenz der glaukomatösen Optikusatrophie in einer arbeitenden Bevölkerungsgruppe [Prevalence of Glaucomatous Optic Nerve Atrophy among a Working Population in Germany Diagnosed by a Telemedical Approach]

Purpose: The aim of this study was to determine the prevalence of glaucomatous optic nerve atrophy among a working population in Germany by secondary evaluation of a study conducted to estimate the prevalence of retinal microangiopathic abnormalities by telemedical examination of the retina. Patients and Methods: From August 2002 until January 2004 the retina and optic nerve head were examined in 19,294 Caucasians using a non-mydriatic fundus camera (Kowa, nonmyd-alpha 45), which produces colour images with 45 degrees. The images of the retina and optic nerve head were evaluated telemedically by glaucoma specialists in respect to optic nerve pathologies and microangiopathic abnormalities by a standardised procedure. Glaucomatous optic nerve atrophy was diagnosed when specific glaucomatous morphological alterations of the optic nerve head were present. A complete medical history including reported elevated intraocular pressure (IOP) and blood pressure was obtained. Results: The intra-observer and inter-observer reliability were 0.884 and 0.740, respectively. Cronbach's alpha for two evaluation cycles each of two observers was 0.870. The prevalences of glaucomatous optic nerve atrophy in the different age groups were 0.07 % (45 - 49 years), 0.40 % (50 - 54 years), 0.45 % (55 - 59 years) and 0.82 % (60 - 64 years). Age could be established as an important risk factor for glaucomatous optic nerve atrophy, while no influence of gender or family history was found. Conclusion: Telemedical evaluation of colour images of the retina and optic nerve acquired by a non-mydriatic fundus camera allows a fast and efficient screening of many subjects with medium reliability

Nimodipine plasma concentration and retinal blood flow in healthy subjects

General view photographed at night 1972

Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy

Transforming growth factor β (TGF-β) has been shown to participate in the pathophysiology of diabetic complications. As shown most recently, TGF-β stimulates the expression of a distinct serine/threonine kinase (hSGK) which had previously been cloned as an early gene transcriptionally regulated by cell volume alterations. The present study was performed to elucidate transcription and function of hSGK in diabetic nephropathy. As shown by Northern blotting, an increase of extracellular glucose concentration increased hSGK mRNA levels in cultured cells, an effect qualitatively mimicked by osmotic cell shrinkage or treatment with TGF-β (2 μg/liter), phorbol 12,13-didecanoate (1 μM), or the Ca(2+) ionophore ionomycin (1 μM) and blunted by high concentrations of nifedipine (10 and 100 μM). In situ hybridization revealed that hSGK transcription was markedly enhanced in diabetic nephropathy, with particularly high expression in mesangial cells, interstitial cells, and cells in thick ascending limbs of Henle's loop and distal tubules. According to voltage clamp and tracer flux studies in Xenopus oocytes expressing the renal epithelial Na(+) channel ENaC or the mouse thick ascending limb Na(+),K(+),2Cl(−) cotransporter BSC-1, coexpression with hSGK stimulated ENaC and BSC-1 11-fold and 6-fold, respectively, effects reversed by kinase inhibitors staurosporine (1 μM) and chelerythrine (1 μM) and not elicited by inactive hSGK. In conclusion, excessive extracellular glucose concentrations enhance hSGK transcription, which in turn stimulates renal tubular Na(+) transport. These observations disclose an additional element in the pathophysiology of diabetic nephropathy