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10.1152/ajprenal.00335.2015

http://scihub22266oqcxt.onion/10.1152/ajprenal.00335.2015
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C4868370!4868370!26672618
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suck abstract from ncbi


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pmid26672618      Am+J+Physiol+Renal+Physiol 2016 ; 310 (5): F385-94
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  • Proximal tubule-targeted heme oxygenase-1 in cisplatin-induced acute kidney injury #MMPMID26672618
  • Bolisetty S; Traylor A; Joseph R; Zarjou A; Agarwal A
  • Am J Physiol Renal Physiol 2016[Mar]; 310 (5): F385-94 PMID26672618show ga
  • Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the breakdown of heme to biliverdin, carbon monoxide, and iron. The beneficial effects of HO-1 expression are not merely due to degradation of the pro-oxidant heme but are also credited to the by-products that have potent, protective effects, including antioxidant, anti-inflammatory, and prosurvival properties. This is well reflected in the preclinical animal models of injury in both renal and nonrenal settings. However, excessive accumulation of the by-products can be deleterious and lead to mitochondrial toxicity and oxidative stress. Therefore, use of the HO system in alleviating injury merits a targeted approach. Based on the higher susceptibility of the proximal tubule segment of the nephron to injury, we generated transgenic mice using cre-lox technology to enable manipulation of HO-1 (deletion or overexpression) in a cell-specific manner. We demonstrate the validity and feasibility of these mice by breeding them with proximal tubule-specific Cre transgenic mice. Similar to previous reports using chemical modulators and global transgenic mice, we demonstrate that whereas deletion of HO-1, specifically in the proximal tubules, aggravates structural and functional damage during cisplatin nephrotoxicity, selective overexpression of HO-1 in proximal tubules is protective. At the cellular level, cleaved caspase-3 expression, a marker of apoptosis, and p38 signaling were modulated by HO-1. Use of these transgenic mice will aid in the evaluation of the effects of cell-specific HO-1 expression in response to injury and assist in the generation of targeted approaches that will enhance recovery with reduced, unwarranted adverse effects.
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