Ubiquitous localization of leukotriene A4 hydrolase in the rat nephron

Nakao, Akihide; Watanabe, Tsuyoshi; Ohishi, Nobuya; Toda, Akiko; Asano, Kenichiro; Taniguchi, Shigeo; Nosaka, Kazuo; Noiri, Eisei; Suzuki, Takehiko; Sakai, Tatsuo; Kurokawa, Kiyoshi; Shimizu, Takao; Kimura, Satoshi

doi:10.1046/j.1523-1755.1999.00257.x

Cited by 18 publications

(24 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the role of these genes in the molecular responses to glomerular toxicity is unclear, the downregulation of some of these genes (i.e., cytosolic epoxide hydrolase, acidic nuclear phosphoprotein 32) was observed at both 24 hr and after 7 days of treatment with 20 mg/kg/day of puromycin. Hydrolases have been identified in rat glomerular mesangial cells and have been implicated in glomerulonephritis (Nakao et al 1999). …”

Section: Discussionmentioning

confidence: 99%

Identification of Putative Gene Based Markers of Renal Toxicity

Amin¹,

Vickers²,

Sistare³

et al. 2004

Environ. Health Perspect.

View full text Add to dashboard Cite

This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants-cisplatin, gentamicin, and puromycin-to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Putative Gene Based Markers of Renal Toxicity

Amin¹,

Vickers²,

Sistare³

et al. 2004

Environ. Health Perspect.

View full text Add to dashboard Cite

show abstract

“…For feeding purposes, ONO-4057 was mixed with rat chow at the concentration of 7 g͞kg, which was continued for more than 4 wk before the start of the experiments to evaluate prefeeding efficacy. The concentration and duration of ONO-4057 feeding were deemed sufficient on the basis of a previously reported study from our laboratory (8).…”

Section: Methodsmentioning

confidence: 99%

An in vivo approach showing the chemotactic activity of leukotriene B ₄ in acute renal ischemic-reperfusion injury

Noiri

Yokomizo

Nakao

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

“…This is not entirely surprising given that the 5-LOX metabolite LTB 4 is a potent chemokine. LTA 4 hydrolase, which converts LTA 4 to LTB 4 , is expressed in the rat nephron (mRNA expression: inner medulla Ͼ outer medulla Ͼ cortical homogenates) (Nakao et al, 1999). Most notably, LTB 4 plays a pivotal role in the recruitment of PMNs in kidneys subjected to I/R, and LTB 4 receptor-antagonists abolish the PMN accumulation after I/R of the kidney (Noiri et al, 2000).…”

Section: -Lipoxygenase In Renal I/r Injury 223mentioning

confidence: 99%

Reduction of Renal Ischemia-Reperfusion Injury in 5-Lipoxygenase Knockout Mice and by the 5-Lipoxygenase Inhibitor Zileuton

Patel¹,

Cuzzocrea²,

Chatterjee³

et al. 2004

Mol Pharmacol

View full text Add to dashboard Cite

The role of 5-lipoxygenase (5-LOX) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Here we investigate the effects of 1) the 5-LOX inhibitor zileuton and 2) 5-LOX gene knockout (5-LOX Ϫ/Ϫ ) mice on renal dysfunction and injury caused by I/R of the kidney in mice. Wild-type mice treated with zileuton (3 mg/kg i.v.) or 5-LOX Ϫ/Ϫ mice were subjected to bilateral renal artery occlusion (30 min) followed by reperfusion (24 h). Plasma urea, creatinine, and aspartate aminotransferase (AST) were measured as markers of renal dysfunction and reperfusion injury. Kidneys were used for histological evaluation of renal injury. Renal myeloperoxidase activity was measured and used as an indicator of polymorphonuclear leukocyte (PMN) infiltration and renal expression of intercellular adhesion molecule-1 (ICAM-1) was determined using immunohistochemistry. Administration of zileuton before I/R significantly reduced the degree of renal dysfunction (urea, creatinine) and injury (AST, histology). In addition, zileuton reduced the expression of ICAM-1 and the associated PMN infiltration caused by I/R of the mouse kidney. Compared with wild-type mice, the degree of renal dysfunction, injury, and inflammation caused by I/R in 5-LOX Ϫ/Ϫ mice was also significantly reduced, confirming the pathophysiological role of 5-LOX in the development of renal I/R injury. We propose that 1) endogenous 5-LOX metabolites enhance the degree of renal injury, dysfunction, and inflammation caused by I/R of the kidney by promoting the expression of adhesion molecules, and 2) inhibitors of 5-LOX may be useful in the treatment of conditions associated with I/R of the kidney.

show abstract

Ubiquitous localization of leukotriene A4 hydrolase in the rat nephron

Abstract: These results strongly suggest that renal tubular cells as well as glomerular cells have an LTB4-forming potency, which may participate in physiological and pathophysiological roles in the kidney.

Cited by 18 publications

References 27 publications

Identification of Putative Gene Based Markers of Renal Toxicity

Identification of Putative Gene Based Markers of Renal Toxicity

An in vivo approach showing the chemotactic activity of leukotriene B ₄ in acute renal ischemic-reperfusion injury

Reduction of Renal Ischemia-Reperfusion Injury in 5-Lipoxygenase Knockout Mice and by the 5-Lipoxygenase Inhibitor Zileuton

Contact Info

Product

Resources

About

Ubiquitous localization of leukotriene A4 hydrolase in the rat nephron

Abstract: These results strongly suggest that renal tubular cells as well as glomerular cells have an LTB4-forming potency, which may participate in physiological and pathophysiological roles in the kidney.

Cited by 18 publications

References 27 publications

Identification of Putative Gene Based Markers of Renal Toxicity

Identification of Putative Gene Based Markers of Renal Toxicity

An in vivo approach showing the chemotactic activity of leukotriene B 4 in acute renal ischemic-reperfusion injury

Reduction of Renal Ischemia-Reperfusion Injury in 5-Lipoxygenase Knockout Mice and by the 5-Lipoxygenase Inhibitor Zileuton

Contact Info

Product

Resources

About

An in vivo approach showing the chemotactic activity of leukotriene B ₄ in acute renal ischemic-reperfusion injury