کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5684925 | 1597924 | 2017 | 46 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Tin protoporphyrin activates the oxidant-dependent NRF2-cytoprotective pathway and mitigates acute kidney injury
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کلمات کلیدی
AKIFeSARFFHCIRI - IRSnPP - SNPPacute kidney injury - آسیب حاد کلیهIschemic reperfusion injury - آسیب مجدد ایسکمیکBUN - خوبFerritin Heavy Chain - زنجیره سنگین فریتینIron sucrose - ساکارز آهنAcute renal failure - نارسایی حاد کلیهblood urea nitrogen - نیتروژن اوره خونheme oxygenase - همگام اکسژنازTin protoporphyrin - پروتپورپیرین قلع
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
پزشکی و دندانپزشکی (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Tin protoporphyrin activates the oxidant-dependent NRF2-cytoprotective pathway and mitigates acute kidney injury Tin protoporphyrin activates the oxidant-dependent NRF2-cytoprotective pathway and mitigates acute kidney injury](/preview/png/5684925.png)
چکیده انگلیسی
Tin protoporphyrin (SnPP), a heme oxygenase (HO) inhibitor, can paradoxically protect against diverse forms of acute kidney injury (AKI). This study sought potential underlying mechanisms. CD-1 mice received intravenous SnPP, followed 4-18 hours later by a variety of renal biochemical, histologic, and genomic assessments. Renal resistance to ischemic-reperfusion injury (IRI) was also sought. SnPP was rapidly taken up by kidney and was confined to proximal tubules. Transient suppression of renal heme synthesis (decreased δ aminolevulinic acid synthase expression), a 2.5-fold increase in “catalytic” Fe levels and oxidant stress resulted (decreased glutathione; increased malondialdehyde, and protein carbonyl content). Nrf2 nuclear translocation (â¼2x Nrf2 increase; detected by enzyme-linked immunosorbent assay, Western blotting), with corresponding activation of â¼20 Nrf2-sensitive genes (RNA-Seq) were observed. By 18 hours after SnPP injection, marked protection against IRI emerged. This represented “preconditioning”, not a direct SnPP effect, given that SnPP administered at the time of IRI exerted no protective effect. The importance of transient oxidant stress in SnPP “preconditioning” was exemplified by the following: (1) oxidant stress induced by a different mechanism (myoglobin injection) recapitulated SnPP's protective action; (2) GSH treatment blunted SnPP's protective influence; (3) SnPP raised cytoprotective heavy chain ferritin (Fhc), a response enhanced by exogenous Fe injection; and (4) SnCl2, a â¼35- to 50-fold HO-1 inducer (not inhibitor) evoked neither oxidant stress nor mitigated IRI (seemingly excluding HO-1 activity in SnPP's protective effect). SnPP specifically accumulates within proximal tubule cells; transient “catalytic” Fe overload and oxidative stress result; Nrf2-cytoprotective pathways are upregulated; and these changes help protect against ischemic AKI.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Translational Research - Volume 186, August 2017, Pages 1-18
Journal: Translational Research - Volume 186, August 2017, Pages 1-18
نویسندگان
Ali C.M. Johnson, Jeff J. Delrow, Richard A. Zager,