Protective effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on glomerular protein permeability barrier

McCarthy, Ellen T.; Sharma, Ram; Sharma, Mukut

doi:10.1111/j.1523-1755.2005.00065.x

Cited by 31 publications

(30 citation statements)

References 37 publications

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“…Similarly, 20-HETE has been reported to oppose the increase in P alb produced by puromycin (12). All of these studies suggest that 20-HETE may have a protective role on the glomerular permeability barrier to oppose the development of a proteinuria and glomerular disease (4,12). However, the role of 20-HETE that is endogenously produced by the glomerulus in the regulation of the glomerular filtration barrier is unknown and was the focus of the present study.…”

Section: Discussionmentioning

confidence: 39%

“…Moreover, our laboratory recently provided evidence that the increase in P alb produced by TGF-␤ (4). Similarly, 20-HETE has been reported to oppose the increase in P alb produced by puromycin (12). All of these studies suggest that 20-HETE may have a protective role on the glomerular permeability barrier to oppose the development of a proteinuria and glomerular disease (4,12).…”

Section: Discussionmentioning

confidence: 93%

“…Previous studies have indicated that increasing the renal formation of 20-HETE and/or EETs protects against the development of hypertension-induced proteinuria and glomerular disease (7,14,20,25,27,28) and that exogenous administration of 20-HETE opposes the effects of TGF-␤ and puromycin to increase P alb (4,12). The present results now extend these findings and indicate that glomeruli normally produce 20-HETE, EETs, diHETEs, and other HETEs and that the endogenous formation of both 20-HETE and EETs plays an essential role in the maintenance of the glomerular permeability barrier to albumin.…”

Section: Perspectivesmentioning

confidence: 99%

“…Exogenous administration of a stable 20-HETE mimetic opposes the effects of TGF-␤ to increase P alb (4). Similarly, 20-HETE has been reported to oppose the increase in P alb following administration of puromycin (12). However, it remains to be determined to what extent cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) are produced by glomeruli and whether they contribute to the maintenance of the glomerular permeability barrier to albumin.…”

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confidence: 99%

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Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier

Sharma

Anjaiahh

Falck³

et al. 2007

American Journal of Physiology-Renal Physiology

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Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier. Am J Physiol Renal Physiol 293: F501-F505, 2007. First published May 16, 2007; doi:10.1152/ajprenal.00131.2007.-This study examined the metabolism of arachidonic acid (AA) by cytochrome P-450 enzymes in isolated glomeruli and the effects of selective inhibitors of the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE) and epoxyeicosatetraenoic acids (EETs) on glomerular permeability to albumin (Palb). Glomeruli avidly produced 20-HETE, EETs, dihydroxyeicosatetraenoic acids (diHETEs), and HETEs when incubated with exogenous AA. N-hydroxy-NЈ-(4-butyl-2-methylphenyl)formamidine (HET0016; 10 M) selectively inhibited the formation of 20-HETE by 95% and increased Palb from 0.00 Ϯ 0.08 to 0.73 Ϯ 0.10 (n ϭ 43 glomeruli, 4 rats). Addition of a 20-HETE mimetic, 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (20-5,14-HEDE; 1 M) opposed the effects of HET0016 (10 M) to increase Palb (0.21 Ϯ 0.10, n ϭ 36 glomeruli, 4 rats). Preincubation of glomeruli with exogenous AA to increase basal production of 20-HETE had a similar effect. We also examined the effect of an epoxygenase inhibitor, N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MSPPOH; 5 M), on Palb. MSPPOH (5 M) significantly increased Palb but had no effect on the synthesis of EETs in glomeruli incubated with AA. However, MSPPOH (5 M) selectively reduced epoxygenase activity by 50% in glomeruli incubated without added AA. Pretreatment with 8,9-EET (100 nM) attenuated the effects of MSPPOH (5 M) on Palb. These results indicate that glomeruli produce 20-HETE, EETs, diHETEs, and HETEs and that endogenously formed 20-HETE and EETs play an essential role in the maintenance of the glomerular permeability barrier to albumin. glomeruli; HET0016; N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide; glomerular permeability to albumin; 20-hydroxyeicosatetraenoic acid; epoxyeicosatetraenoic acids HYPERTENSION-AND DIABETES-INDUCED NEPHROPATHIES are the leading causes of end-stage renal disease (3,16,22). Elevations in glomerular capillary pressure are thought to contribute to the development of proteinuria in these conditions (5,6,11,21,24,31), but the mechanisms involved are not well understood. A rise in glomerular capillary pressure may contribute to the development of renal injury by increasing the production of transforming growth factor-␤ (TGF-␤) (1, 18). TGF-␤ is now known to increase glomerular permeability to albumin (P alb ), and this is associated with a fall in the endogenous formation of 20-HETE (4). Exogenous administration of a stable 20-HETE mimetic opposes the effects of TGF-␤ to increase P alb (4). Similarly, 20-HETE has been reported to oppose the increase in P alb following administration of puromycin (12). However, it remains to be determined to what extent cytochrome P-450 (CYP) metabolites of arachidonic acid (AA) are produced by glomeruli and whether they contribute to the maintenance of the glomerular permeability barrier to albumin. Th...

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Section: Discussionmentioning

confidence: 39%

Section: Discussionmentioning

confidence: 93%

Section: Perspectivesmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier

Sharma

Anjaiahh

Falck³

et al. 2007

American Journal of Physiology-Renal Physiology

Self Cite

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“…In other words, microalbuminuria should just be a very transient and initial event in this condition. Also, a number of previous in vitro studies on isolated glomeruli indicate that glomerular permeability can indeed increase very rapidly and transiently (within 5-15 min) in response to various challenges, such as puromycin aminonucleoside (PAN), TNF-␣, vascular endothelial growth factor, or transforming growth factor (3,13,14,26,28). In isolated glomeruli in vitro, the acute permeability effects of TNF-␣ and PAN were found to be mediated in part by reactive oxygen species, since inhibition of these, or their generation, apparently reduced the changes in glomerular permeability (13).…”

Section: Discussionmentioning

confidence: 99%

Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats

Axelsson

Rippe²,

Venturoli³

et al. 2009

American Journal of Physiology-Renal Physiology

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Axelsson J, Rippe A, Venturoli D, Swärd P, Rippe B. Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats. Am J Physiol Renal Physiol 296: F242-F248, 2009. First published November 12, 2008 doi:10.1152/ajprenal.90263.2008.-This study was performed to investigate the glomerular permeability alterations responsible for the microalbuminuria occurring in endotoxemia and during anaphylactic shock. In anesthetized Wistar rats, the left ureter was catheterized for urine collection while, simultaneously, blood access was achieved. Endotoxemia was induced by lipopolysaccharide (LPS) from Escherichia coli, and glomerular permeability was assessed at 60 and 90 (n ϭ 7) and 120 (n ϭ 7) min. Anaphylaxis was induced by a bolus dose of Dextran-70, and glomerular permeability assessed at 5 min (n ϭ 8) and 40 min (n ϭ 9). Sham animals were followed for either 5 or 120 min. The glomerular sieving coefficients () to fluorescein isothiocyanate-Ficoll (70/400) were determined from plasma and urine samples and assessed using size-exclusion chromatography (HPLC). After start of the LPS infusion (2 h), but not at 60 or 90 min, for Ficoll70Å had increased markedly [from 2.91 ϫ 10 Ϫ5 Ϯ 6.33 ϫ 10 Ϫ6 to 7.78 ϫ 10 Ϫ5 Ϯ 6.21 ϫ 10 Ϫ6 (P Ͻ 0.001)]. In anaphylaxis, there was a large increase in for Ficolls Ͼ60 Å in molecular radius already at 5 min, but the glomerular permeability was completely restored at 40 min. In conclusion, there was a transient, immediate increment of glomerular permeability in dextran-induced anaphylaxis, which was completely reversible within 40 min. By contrast, endotoxemia caused an increase in glomerular permeability that was manifest first after 2 h. In both cases, to large Ficoll molecules were markedly increased, reflecting an increase in the number of large pores in the glomerular filter. endotoxin; systemic inflammatory response syndrome MICROALBUMINURIA, I.E., JUST moderately increased urinary albumin excretion rates (20 -200 g/min in humans), is an early predictor of many glomerular diseases, such as various glomerulonephritides and diabetic nephropathy and is an established marker of endothelial dysfunction. It is also a feature of acute systemic inflammation or stress, such as following trauma (18), operations (6, 16), thermal injury (30), or in the systemic inflammatory response syndrome (SIRS) (4). The pathophysiological alterations resulting in microalbuminuria have only rarely been investigated. For example, it is not precisely known whether (proximal) tubular dysfunction is the major cause of microalbuminuria or whether charge-or sizeselective alterations of the glomerular filtration barrier, or both, are affected. In a recent study, we found that early diabetic microalbuminuria in rats was mainly related to size-selective changes in the glomerular barrier (25) and that charge alterations were just secondary. Also, the glomerular alterations following pronounced ischemia-reperfusion (I/R) injury could be mainly ascribed to siz...

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The Urine Proteome as a Radiation Biodosimeter

Sharma

Moulder

2013

Advances in Experimental Medicine and Biology

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The global rise in terrorism has increased the risk of radiological events aimed at creating chaos and destabilization, although they may cause relatively limited number of immediate casualties. We have proposed that a self-administered test would be valuable for initial triage following terrorist use of nuclear/radiological devices. The urine proteome may be a useful source of the biomarkers required for developing such a test. We have developed and extensively used a rat model to study the acute and late effect of total body (TBI) and partial body irradiation on critical organ systems. This model has proven valuable for correlating the structural and functional effects of radiation with molecular changes. Results show that nephron segments differ with regard to their sensitivity and response to ionizing radiation. The urine proteome was analyzed using LC-MS/MS at 24 h after TBI or local kidney irradiation using a 10 Gy single dose of X rays. LC-MS/MS data were analyzed and grouped under Gene Ontology categories Cellular Localization, Molecular Function and Biological Process. We observed a decrease in urine protein/creatinine ratio that corroborated with decreased spectral counts for urinary albumin and other major serum proteins. Interestingly, TBI caused greater decline in urinary albumin than local kidney irradiation. Analysis of acute-phase response proteins and markers of acute kidney injury showed increased urinary levels of cystatin superfamily proteins and alpha-1-acid glycoprotein. Among proteases and protease inhibitors, levels of Kallikrein 1-related peptidase b24, precursor and products of chymotrypsin-like activity, were noticeably increased. Among the amino acids that are susceptible to oxidation by free radicals, oxidized histidine levels were increased following irradiation. Our results suggest that proteomic analysis of early changes in urinary proteins will identify biomarkers for developing a self-administered test for radiation biodosimetry.

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Protective effect of 20-hydroxyeicosatetraenoic acid (20-HETE) on glomerular protein permeability barrier

Cited by 31 publications

References 37 publications

Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier

Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier

Effects of early endotoxemia and dextran-induced anaphylaxis on the size selectivity of the glomerular filtration barrier in rats

The Urine Proteome as a Radiation Biodosimeter

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