Hydroxyl Radicals Depolymerize Glomerular Heparan Sulfate in Vitro and in Experimental Nephrotic Syndrome

Raats, C.J.I.; Bakker, Marinka A.H.; Born, J. van den; Berden, J.H.M.

doi:10.1074/jbc.272.42.26734

Cited by 105 publications

(95 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The increased expression of heparanase in AN is in line with the findings in puromycin aminonucleoside nephrosis, passive Heymann nephritis, and anti-GBM nephritis (15)(16)(17)(18). The loss of glomerular HS also is in accordance with previous studies in proteinuric renal disease (7)(8)(9). Our data on a consistent association between HS and heparanase suggest that heparanase is an important factor involved in the breakdown of HS and thereby in the development of proteinuria.…”

Section: Discussionsupporting

confidence: 80%

“…In Adriamycin nephrop-athy (AN), a model of chronic proteinuric renal damage (19), we previously reported a decrease of HS expression, which was caused partially by hydroxyl radicals (7). Furthermore, we found that RAS blockade protects against loss of HS in established AN (9).…”

mentioning

confidence: 92%

“…Third, loss of anionic HS has been reported in several human and experimental glomerulopathies, which was inversely correlated with the degree of proteinuria (5,6). It is suggested that proteinuriainduced renal damage is associated with loss of glomerular HS in diabetic and nondiabetic renal disease (7)(8)(9).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Kramer¹,

Hoven²,

Rops³

et al. 2006

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Heparan sulfate (HS) in the glomerular basement membrane (GBM) is important for regulation of the charge-dependent permeability. Heparanase has been implicated in HS degradation in several proteinuric diseases. This study analyzed the role of heparanase in HS degradation in Adriamycin nephropathy (AN), a model of chronic proteinuria-induced renal damage. Expression of heparanase, HS, and the core protein of agrin (to which HS is attached) was determined on kidney sections from rats with AN in different experiments. First, expression was examined in a model of unilateral AN in a time-course study at 6-wk intervals until week 30. Second, rats were treated with the hydroxyl radical scavenger dimethylthiourea (DMTU) during bilateral AN induction. Finally, 6 wk after AN induction, rats were treated with angiotensin II receptor type 1 antagonist (AT1A) or vehicle for 2 wk. Heparanase expression was increased in glomeruli of rats with AN, which correlated with HS reduction at all time points and in all experiments. Treatment with DMTU prevented the increased heparanase expression, the loss of GBM HS, and reduced albuminuria. Finally, treatment of established proteinuria with AT1A significantly reduced heparanase expression and restored glomerular HS. In conclusion, an association between heparanase expression and reduction of glomerular HS in AN was observed. The effects of DMTU suggest a role for reactive oxygen species in upregulation of heparanase. Antiproteinuric treatment by AT1A decreased heparanase expression and restored HS expression. These results suggest involvement of radicals and angiotensin II in the modulation of GBM permeability through HS and heparanase expression.

show abstract

Section: Discussionsupporting

confidence: 80%

mentioning

confidence: 92%

See 1 more Smart Citation

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Kramer¹,

Hoven²,

Rops³

et al. 2006

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

show abstract

“…HS content was determined as previously described with HS ELISA kit (Seikagaku) (36). Cells were collected and disrupted by sonication followed by centrifugation at 14,000 rpm for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Epac increases melanoma cell migration by a heparan sulfate-related mechanism

Baljinnyam

Iwatsubo

Kurotani

et al. 2009

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

2009.-Melanoma, the most malignant form of human skin cancer, has a poor prognosis due to its strong metastatic ability. It was recently demonstrated that Epac, an effector molecule of cAMP, is involved in regulating cell migration; however, the role of Epac in melanoma cell migration remains unclear. We thus examined whether Epac regulates cell migration and metastasis of melanoma. Epac activation, by either specific agonist or overexpression of Epac, increased melanoma cell migration. Deletion of endogenous Epac with small interfering RNA decreased basal melanoma cell migration. These data suggested a major role of Epac in melanoma cell migration. Epac-induced cell migration was mediated by translocation of syndecan-2, a cell-surface heparan sulfate proteoglycan, to lipid rafts. This syndecan-2 translocation was regulated by tubulin polymerization via the Epac/phosphoinositol-3 kinase pathway. Epacinduced cell migration was also regulated by the production of heparan sulfate, a major extracellular matrix. Epac-induced heparan sulfate production was attributable to the increased expression of N-deacetylase/N-sulfotransferase-1 (NDST-1) accompanied by an increased NDST-1 translation rate. Finally, Epac overexpression enhanced lung colonization of melanoma cells in mice. Taken together, these data indicate that Epac regulates melanoma cell migration/ metastasis mostly via syndecan-2 translocation and heparan sulfate production. metastasis; phosphoinositol-3 kinase; N-deacetylase/N-sulfotransferase-1

show abstract

“…Injuries to the basement membrane can result in the release of these pro-invasive compounds. Furthermore, fragmentation of matrix proteins by free radicals or limited proteolysis can generate biologically active peptides, that is, the matrikines (Vartio 1989;Monboisse and Borel 1992;Raats et al, 1997;Duca et al, 2004). Once released, these matrikines, such as elastin peptides, can increase the expression of MMP-2, MT1-MMP and TIMP-2 in fibrosarcoma HT-1080 cells (Brassart et al, 1998).…”

mentioning

confidence: 99%

In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells

et al. 2007

View full text Add to dashboard Cite

Following removal of the primary breast tumour by conservative surgery, patients may still have additional malignant foci scattered throughout the breast. Radiation treatments are not designed to eliminate all these residual cancer cells. Rather, the radiation dose is calculated to optimise long-term results with minimal complications. In a tumour, cancer cells are surrounded by a basement membrane, which plays an important role in the regulation of gene expression. Using an invasion chamber, we have shown that irradiation before cell plating of a reconstituted basement membrane (Matrigel; Becton Dickinson, Bedford, MA, USA) increased the invasiveness of the breast cancer cells MDA-MB-231. This radiation enhancement of invasion was associated with the upregulation of the pro-invasive gene matrix metalloproteinase (MMP)-2. The expression of membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitor of metalloproteinase-2 (TIMP), which are required to activate the MMP-2, were also increased. Confirming the role of MMP-2 and MT1-MMP, radiation enhancement of cancer cell invasion was prevented by an MMP-2 inhibitor and an anti-MT1-MMP antibody. This study also demonstrated that radiation can potentially enhance the invasion ability by inducing the release of pro-invasive factors stored in the Matrigel. Conversely, no enhancement of invasiveness was observed with the low metastatic cell line MCF-7. This lack of invasiveness correlated with the absence of the MMP-2 activator MT1-MMP in the MCF-7 cells. Radiotherapy is an efficient modality to treat breast cancer which could be further improved by inhibiting the pro-invasive gene upregulated by radiation.

show abstract

Hydroxyl Radicals Depolymerize Glomerular Heparan Sulfate in Vitro and in Experimental Nephrotic Syndrome

Cited by 105 publications

References 44 publications

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System

Epac increases melanoma cell migration by a heparan sulfate-related mechanism

In vitro irradiation of basement membrane enhances the invasiveness of breast cancer cells

Contact Info

Product

Resources

About