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10.1016/j.bcmd.2014.12.001

http://scihub22266oqcxt.onion/10.1016/j.bcmd.2014.12.001
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C4338572!4338572!25582460
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suck abstract from ncbi


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pmid25582460      Blood+Cells+Mol+Dis 2015 ; 54 (3): 302-6
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  • Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubules cells and kidneys of a mouse model of sickle cell disease #MMPMID25582460
  • Chintagari NR; Nguyen J; Belcher JD; Vercellotti GM; Alayash AI
  • Blood Cells Mol Dis 2015[Mar]; 54 (3): 302-6 PMID25582460show ga
  • Sickle cell disease (SCD), a hereditary hemolytic disorder is characterized by chronic hemolysis, oxidative stress, vaso-occlusion and end-organ damage. Hemolysis releases toxic cell-free hemoglobin (Hb) into circulation. Under physiologic conditions, plasma Hb binds to haptoglobin (Hp) and forms Hb-Hp dimers. The dimers bind to CD163 receptors on macrophages for further internalization and degradation. However, in SCD patients plasma Hp is depleted and free Hb is cleared primarily by proximal tubules of kidneys. Excess free Hb in plasma predisposes patients to renal damage. We hypothesized that administration of exogenous Hp reduces Hb-mediated renal damage. To test this hypothesis, human renal proximal tubular cells (HK-2) were exposed to HbA (50 ?M heme) for 24 hours. HbA increased the expression of heme oxygenase-1 (HO-1), an enzyme which degrades heme, reduces heme-mediated oxidative toxicity, and confers cytoprotection. Similarly, infusion of HbA (32 ?M heme/kg) induced HO-1 expression in kidneys of SCD mice. Immunohistochemistry confirmed the increased HO-1 expression in the proximal tubules of the kidney. Exogenous Hp attenuated the HbA-induced HO-1 expression in vitro and in SCD mice. Our results suggest that Hb-mediated oxidative toxicity may contribute to renal damage in SCD and that Hp treatment reduces heme/iron toxicity in the kidneys following hemolysis.
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