Ultracytochemical localization of Ca 2+ -ATPase activity in the endolymphatic sac of the chick

Yoshihara, Toshio; Satoh, Michiko; Igarashi, Makoto

doi:10.1007/s007950000012

Cited by 5 publications

(3 citation statements)

References 13 publications

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“…Morphologically, diabetic mice with Sema3a + gain of function developed mesangiolysis and nodular glomerulosclerosis in >50% of glomeruli, extensive mesangial sclerosis, and interstitial fibrosis within 12–16 weeks. Moreover, Sema3a + gain-of-function glomerular histology and TEM revealed multiple features of human advanced diabetic nephropathy ( 34 ), including diffuse GBM thickening, widespread effacement and fusion of podocyte foot processes, marked podocytopenia, Kimmelstiel-Wilson-like nodular lesions, endothelial injury, fibrin caps, and vascular pole hyalinosis. Few mouse models of diabetic nephropathy have developed diabetic nodular glomerulosclerosis, namely eNOS knockout ( 35 , 36 ), β-cell calmodulin transgenics ( 37 , 38 ), podocyte- VEGF-A gain-of-function ( 24 ), and BTBR Ob/Ob mice ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Semaphorin3a Promotes Advanced Diabetic Nephropathy

et al. 2014

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The onset of diabetic nephropathy (DN) is highlighted by glomerular filtration barrier abnormalities. Identifying pathogenic factors and targetable pathways driving DN is crucial to developing novel therapies and improving the disease outcome. Semaphorin3a (sema3a) is a guidance protein secreted by podocytes. Excess sema3a disrupts the glomerular filtration barrier. Here, using immunohistochemistry, we show increased podocyte SEMA3A in renal biopsies from patients with advanced DN. Using inducible, podocyte-specific Sema3a gain-of-function (Sema3a+) mice made diabetic with streptozotocin, we demonstrate that sema3a is pathogenic in DN. Diabetic Sema3a+ mice develop massive proteinuria, renal insufficiency, and extensive nodular glomerulosclerosis, mimicking advanced DN in humans. In diabetic mice, Sema3a+ exacerbates laminin and collagen IV accumulation in Kimmelstiel-Wilson-like glomerular nodules and causes diffuse podocyte foot process effacement and F-actin collapse via nephrin, αvβ3 integrin, and MICAL1 interactions with plexinA1. MICAL1 knockdown and sema3a inhibition render podocytes not susceptible to sema3a-induced shape changes, indicating that MICAL1 mediates sema3a-induced podocyte F-actin collapse. Moreover, sema3a binding inhibition or podocyte-specific plexinA1 deletion markedly ameliorates albuminuria and abrogates renal insufficiency and the diabetic nodular glomerulosclerosis phenotype of diabetic Sema3a+ mice. Collectively, these findings indicate that excess sema3a promotes severe diabetic nephropathy and identifies novel potential therapeutic targets for DN.

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Section: Discussionmentioning

confidence: 99%

Semaphorin3a Promotes Advanced Diabetic Nephropathy

et al. 2014

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“…Morphological and ultrastructural changes of the mitochondria in proximal tubules correlate with deterioration of renal function in diabetes [33], [34]. Increased posttranslational modification of renal mitochondrial proteins through glycation [35], nitration and oxidation [36] is associated with the development of diabetic nephropathy in animal models.…”

Section: Discussionmentioning

confidence: 99%

Geldanamycin Derivative Ameliorates High Fat Diet-Induced Renal Failure in Diabetes

et al. 2012

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Diabetic nephropathy is a serious complication of longstanding diabetes and its pathogenesis remains unclear. Oxidative stress may play a critical role in the pathogenesis and progression of diabetic nephropathy. Our previous studies have demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite generation in primary human kidney mesangial cells and heat shock protein 90β1 (hsp90β1) is indispensable for the PUFA action. Here we investigated the effects of high fat diet (HFD) on kidney function and structure of db/db mice, a widely used rodent model of type 2 diabetes. Our results indicated that HFD dramatically increased the 24 h-urine output and worsened albuminuria in db/db mice. Discontinuation of HFD reversed the exacerbated albuminuria but not the increased urine output. Prolonged HFD feeding resulted in early death of db/db mice, which was associated with oliguria and anuria. Treatment with the geldanamycin derivative, 17-(dimethylaminoehtylamino)-17-demethoxygeldanamycin (17-DMAG), an hsp90 inhibitor, preserved kidney function, and ameliorated glomerular and tubular damage by HFD. 17-DMAG also significantly extended survival of the animals and protected them from the high mortality associated with renal failure. The benefit effect of 17-DMAG on renal function and structure was associated with a decreased level of kidney nitrotyrosine and a diminished kidney mitochondrial Ca2+ efflux in HFD-fed db/db mice. These results suggest that hsp90β1 is a potential target for the treatment of nephropathy and renal failure in diabetes.

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“…5 Calcium metabolism in the inner ear is tightly regulated through calcium channels and Ca ++ -ATPase at concentrations that are low in the endolymph and high in the perilymph. 2,[6][7][8][9][10][11][12][13] In vivo detection of Ca ++ handling in the inner ear is valuable for both research and the clinical diagnosis of inner ear disease at an early stage. However, this technique is not yet available.…”

Section: Introductionmentioning

confidence: 99%

Calcium Metabolism Profile in Rat Inner Ear Indicated by MRI After Tympanic Medial Wall Administration of Manganese Chloride

Zou

Pyykkö

2015

Ann Otol Rhinol Laryngol

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Objectives: To evaluate the efficacy of the novel method for the targeted delivery of Mn ++ to the inner ear and monitor calcium metabolism activity in the inner ear. Materials and Methods: Dynamic signal changes of Mn ++ in the rat inner ear were followed using T 1 -weighted magnetic resonance imaging (MRI) after administration of 2.5 µl MnCl 2 (500 mM) to the medial wall of the middle ear cavity. Results: Mn ++ passed through both the oval and round windows and distributed in the perilymphatic compartments, where it formed bright sharp lines along the fluid-cellular borders 12 minutes post administration and entered the endolymph sufficiently after 45 minutes. After 6 hours, the distribution of Mn ++ shifted from a fluid-dominant pattern to a cell-dominant pattern. Mn ++ concentrated in the area of the basilar membrane, periphery process, and soma of the spiral ganglion on day 2; became more distinguishable on day 4; declined on day 8; and remained detectable for 16 days post administration. Conclusions:The novel targeted delivery method efficiently introduced Mn ++ into the inner ear. The dynamic distribution pattern of Mn ++ in the inner ear shown by MRI indicates that this method can be used to monitor calcium metabolism activity in the inner ear.

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Ultracytochemical localization of Ca 2+ -ATPase activity in the endolymphatic sac of the chick

Cited by 5 publications

References 13 publications

Semaphorin3a Promotes Advanced Diabetic Nephropathy

Semaphorin3a Promotes Advanced Diabetic Nephropathy

Geldanamycin Derivative Ameliorates High Fat Diet-Induced Renal Failure in Diabetes

Calcium Metabolism Profile in Rat Inner Ear Indicated by MRI After Tympanic Medial Wall Administration of Manganese Chloride

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