Alterations of the podocyte proteome in response to high glucose concentrations

Schordan, Sandra; Schordan, Eric; Endlich, Nicole; Lindenmeyer, Maja T.; Meyer-Schwesinger, Catherine; Meyer, Tobias; Giebel, J.; Cohen, Clemens D.; Endlich, Karlhans; Maurer, Martin H.

doi:10.1002/pmic.200800214

Cited by 29 publications

(28 citation statements)

References 32 publications

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“…Podocytes utilize their dynamic cytoskeleton to maintain their complex shape and function [30] and a very recent proteomic analysis demonstrated that numerous cytoskeletal proteins are altered as a consequence of high-glucose exposure [31]. As in neuronal cells, the influence of actin dynamics on cell health is especially relevant along cell processes and our data highlight this as there was no difference in actin distribution in the cell body but a specific alteration of actin dynamics along podocyte processes was found.…”

Section: Discussionsupporting

confidence: 52%

Proteinuria and Glomerular Damage in Rab3A Knockout Mice Chronically Fed a High-Glucose Diet

Armelloni

Calvaresi

Ikehata

et al. 2012

Nephron Exp Nephrol

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Background/Aims: The relative contribution of genetic factors and dietary patterns to glomerular damage in healthy individuals and prediabetic conditions is currently unclear. All Rab3A knockout (KO) mice spontaneously develop macroalbuminuria, but only male mice exhibit a glucose-intolerant phenotype, thus making the model suitable to examine the impact of a diet on preexisting podocyte damage. Methods: Male and female Rab3A KO and wild-type (WT) mice were chronically fed a high-glucose diet (HGD). Biochemical tests, histology and immunohistochemistry were periodically performed whilst primary podocytes served for in vitro analyses. Results: Chronic administration of an HGD did not induce de novo alterations in WT kidneys but caused progressive worsening of podocyte and glomerular damage in both male and female Rab3A KO. Though glomerular lesions, reminiscent of human diabetic nephropathy, were more severe in male mice, overt proteinuria and renal damage were also evident in female mice. The in vitro analysis of Rab3A WT and KO podocytes revealed diminished actin plasticity in the cell processes of KO podocytes. Furthermore, a modest increase in glucose concentration induced profound cytoskeletal changes only in Rab3A KO cells. Conclusions: Our data show that chronic administration of an HGD to Rab3A KO mice that have a genetic defect that impairs podocyte actin plasticity results in increased podocyte damage and leads to overt proteinuria. If the same diet is given to male Rab3A KO animals, with additionally altered glucose homeostasis, this results in renal lesions similar to those of human diabetic nephropathy.

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Section: Discussionsupporting

confidence: 52%

Proteinuria and Glomerular Damage in Rab3A Knockout Mice Chronically Fed a High-Glucose Diet

Armelloni

Calvaresi

Ikehata

et al. 2012

Nephron Exp Nephrol

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“…Furthermore, one current study showed differential proteomic changes in an immortalized mouse podocyte cell line after long term exposure (two weeks) to HG (Schordan et al 2009). However, our study of primary cultured rat GECs exposed to HG for three days demonstrated different patterns of proteome changes compared with the above cited study.…”

Section: Discussionmentioning

confidence: 67%

Hyperglycemia Decreases the Expression of ATP Synthase <b><i>β</i></b> Subunit and Enolase 2 in Glomerular Epithelial Cells

Hwang

Kwon

Kim

et al. 2013

Tohoku J. Exp. Med.

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Glomerular epithelial cells (GECs) are known to play a key role in maintaining the structure and function of the glomerulus. GEC injury induced by hyperglycemia is present in early-stage diabetic nephropathy (DN), which is the most common cause of renal failure. In an attempt to identify target proteins involved in the pathogenesis of GEC injury at early DN, we performed the proteomic analysis using primary cultures of GECs, prepared from the dissected rat glomeruli. The protein expression profiles in the two-dimensional electrophoresis gels were compared between GECs treated for three days with normal glucose (5 mM) and those with high glucose (30 mM) concentrations. These concentrations correspond to blood glucose concentrations under normoglycemia and hyperglycemia, respectively. Proteins with differential expression levels were identified using ESI-Q-TOF tandem mass spectrometry. The primary GECs cultured in hyperglycemic conditions showed cellular hypertrophy and increased production of reactive oxygen species, both of which reflect the GEC injury. Our proteomic analysis identified eight proteins with differential expression profiles, depending on glucose concentrations. Among them, we selected ATP synthase β subunit and enolase 2 that are related to energy metabolism and are down-regulated under hyperglycemia, and confirmed that hyperglycemia decreased the expression levels of ATP synthase β subunit and enolase 2 proteins by western blotting analysis. Hyperglycemia may impair mitochondrial function and alter glycolysis in GECs by down-regulating the expression of ATP synthase β subunit and enolase 2. The present study may provide a better understanding of the pathogenic mechanisms of GEC injury in early DN.

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“…Schordan et al observed changes in cytoskeletal proteins in cultured human podocytes under high glucose conditions and found similar changes in biopsies from patients with diabetic nephropathy 65 . Recently, we performed a proteome analysis of early and late proximal tubules prepared by hand-dissection from control animals and acidotic mice and assessed changes in protein expression by adding kidney tissue from SILAC mice (Velic, Macek, Nowik, Mann, Wagner, unpublished results).…”

Section: Application Of Proteomics To Normal and Diseased Kidney Funcmentioning

confidence: 88%

“…Substructures of glomeruli or the component of the glomerular filtration barrier, i.e. podocytes, mostly originating from the cell culture have also been investigated 65 .…”

Section: Segment-directed Proteomics In the Nephron/kidneymentioning

confidence: 99%

Toward Quantitative Proteomics of Organ Substructures: Implications for Renal Physiology

Velić

Maček

Wagner

2010

Seminars in Nephrology

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AcknowledgementsResearch in the laboratories of the authors has been supported by grants from the Minstry of Science, Baden-Wuerttenberg (to BM) and the Swiss National Science Foundation, the 6 th and 7 th EU Framework projects (EuReGene and EUNEFRON) (to CAW). We thank MatthiasMann for critically reading and discussing the manuscript. Summary 2Organs are complex structures that consist of multiple tissues with different levels of gene expression. To achieve a comprehensive coverage and accurate quantitation data, organs should ideally be separated into morphological and/or functional substructures prior to gene or protein expression analysis. However, due to complex morphology and elaborate isolation protocols, this was so far often difficult to achieve. Kidneys are organs where functional and morphological subdivision is especially important. Each subunit of the kidney, the nephron, itself consists of more than 10 subsegments with distinct morphological and functional characteristics. For a full understanding of kidney physiology, global gene and protein expression analyses have to be performed at the level of the nephron subsegments; however, such studies have so far been extremely rare.Here we describe the latest approaches in quantitative high accuracy mass spectrometrybased proteomics and their application to quantitative proteomics studies of the whole kidney and nephron subsegments, both in humans and in animal models. We compare these studies with similar studies performed on other organ substructures. We argue that the newest technologies used for preparation, processing and measurement of small amounts of starting material are finally enabling global and subsegment-specific quantitative measurement of protein levels in the kidney and other organs. These new technologies and approaches are making a decisive impact on our understanding of the (patho)physiological processes at the molecular level.3

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Alterations of the podocyte proteome in response to high glucose concentrations

Cited by 29 publications

References 32 publications

Proteinuria and Glomerular Damage in Rab3A Knockout Mice Chronically Fed a High-Glucose Diet

Proteinuria and Glomerular Damage in Rab3A Knockout Mice Chronically Fed a High-Glucose Diet

Hyperglycemia Decreases the Expression of ATP Synthase <b><i>β</i></b> Subunit and Enolase 2 in Glomerular Epithelial Cells

Toward Quantitative Proteomics of Organ Substructures: Implications for Renal Physiology

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