Deficiency in the Formation of 20-Hydroxyeicosatetraenoic Acid Enhances Renal Ischemia-Reperfusion Injury
Copyright © 2015 by the American Society of Nephrology..
Ischemia-reperfusion (IR) injury is the most common cause of AKI. The susceptibility to develop AKI varies widely among patients. However, little is known about the genes involved. 20-Hydroxyeicosatetraenoic acid (20-HETE) has an important role in the regulation of renal tubular and vascular function and has been implicated in IR injury. In this study, we examined whether a deficiency in the renal formation of 20-HETE enhances the susceptibility of Dahl salt-sensitive (SS) rats to ischemic AKI. Transfer of chromosome 5 containing the CYP4A genes responsible for the formation of 20-HETE from the Brown Norway (BN) rat onto the SS genetic background increased renal 20-HETE levels after ischemia and reduced plasma creatinine levels (±SEM) 24 hours after IR from 3.7±0.1 to 2.0±0.2 mg/dl in an SS.5(BN)-consomic strain. Transfer of this chromosome also prevented the secondary decline in medullary blood flow and ischemia that develops 2 hours after IR in the susceptible SS strain. Blockade of the synthesis of 20-HETE with HET0016 reversed the renoprotective effects in SS.5(BN) rats. Similar results were observed in an SS.5(Lew)-congenic strain, in which a smaller region of chromosome 5 containing the CYP4A genes from a Lewis rat was introgressed onto the SS genetic background. These results indicate that 20-HETE has a protective role in renal IR injury by maintaining medullary blood flow and that a genetic deficiency in the formation of 20-HETE increases the susceptibility of SS rats to ischemic AKI.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2015 |
|---|---|
| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
|---|---|
| Enthalten in: |
Journal of the American Society of Nephrology : JASN - 26(2015), 10 vom: 28. Okt., Seite 2460-9 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Muroya, Yoshikazu [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 31.12.2015 Date Revised 23.02.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1681/ASN.2014090868 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM245875867 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM245875867 | ||
| 003 | DE-627 | ||
| 005 | 20231224141831.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2015 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1681/ASN.2014090868 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0819.xml |
| 035 | |a (DE-627)NLM245875867 | ||
| 035 | |a (NLM)25644108 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Muroya, Yoshikazu |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Deficiency in the Formation of 20-Hydroxyeicosatetraenoic Acid Enhances Renal Ischemia-Reperfusion Injury |
| 264 | 1 | |c 2015 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 31.12.2015 | ||
| 500 | |a Date Revised 23.02.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2015 by the American Society of Nephrology. | ||
| 520 | |a Ischemia-reperfusion (IR) injury is the most common cause of AKI. The susceptibility to develop AKI varies widely among patients. However, little is known about the genes involved. 20-Hydroxyeicosatetraenoic acid (20-HETE) has an important role in the regulation of renal tubular and vascular function and has been implicated in IR injury. In this study, we examined whether a deficiency in the renal formation of 20-HETE enhances the susceptibility of Dahl salt-sensitive (SS) rats to ischemic AKI. Transfer of chromosome 5 containing the CYP4A genes responsible for the formation of 20-HETE from the Brown Norway (BN) rat onto the SS genetic background increased renal 20-HETE levels after ischemia and reduced plasma creatinine levels (±SEM) 24 hours after IR from 3.7±0.1 to 2.0±0.2 mg/dl in an SS.5(BN)-consomic strain. Transfer of this chromosome also prevented the secondary decline in medullary blood flow and ischemia that develops 2 hours after IR in the susceptible SS strain. Blockade of the synthesis of 20-HETE with HET0016 reversed the renoprotective effects in SS.5(BN) rats. Similar results were observed in an SS.5(Lew)-congenic strain, in which a smaller region of chromosome 5 containing the CYP4A genes from a Lewis rat was introgressed onto the SS genetic background. These results indicate that 20-HETE has a protective role in renal IR injury by maintaining medullary blood flow and that a genetic deficiency in the formation of 20-HETE increases the susceptibility of SS rats to ischemic AKI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 20-HETE | |
| 650 | 4 | |a AKI | |
| 650 | 4 | |a genetics | |
| 650 | 4 | |a intrarenal blood flow | |
| 650 | 7 | |a Hydroxyeicosatetraenoic Acids |2 NLM | |
| 650 | 7 | |a 20-hydroxy-5,8,11,14-eicosatetraenoic acid |2 NLM | |
| 650 | 7 | |a 79551-86-3 |2 NLM | |
| 650 | 7 | |a Cytochrome P-450 CYP4A |2 NLM | |
| 650 | 7 | |a EC 1.14.15.3 |2 NLM | |
| 700 | 1 | |a Fan, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Regner, Kevin R |e verfasserin |4 aut | |
| 700 | 1 | |a Falck, John R |e verfasserin |4 aut | |
| 700 | 1 | |a Garrett, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Juncos, Luis A |e verfasserin |4 aut | |
| 700 | 1 | |a Roman, Richard J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of the American Society of Nephrology : JASN |d 1990 |g 26(2015), 10 vom: 28. Okt., Seite 2460-9 |w (DE-627)NLM012606502 |x 1533-3450 |7 nnns |
| 773 | 1 | 8 | |g volume:26 |g year:2015 |g number:10 |g day:28 |g month:10 |g pages:2460-9 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1681/ASN.2014090868 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 26 |j 2015 |e 10 |b 28 |c 10 |h 2460-9 | ||