Poly(ethylene glycol) cross-linked hemoglobin with antioxidant enzymes protects pancreatic islets from hypoxic and free radical stress and extends islet functionality.

Poly(ethylene glycol) cross-linked hemoglobin with antioxidant enzymes protects pancreatic islets from hypoxic and free radical stress and extends islet functionality.
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DOI:
10.1002/bit.24501
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发表时间:
2012-09
影响因子:
3.8
通讯作者:
Bae, You Han
Bae, You Han
中科院分区:
工程技术2区
文献类型:
--
作者:
Nadithe, Venkatareddy;Mishra, Deepa;Bae, You Han

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The objective of this study was to investigate the efficiency of multifunctional PEG-based hemoglobin conjugates crosslinked with antioxidant enzymes for their ability to protect an oxygen carrier (hemoglobin) and insulin secreting islets from the combination of hypoxic and free radical stress under simulated transplantation conditions. In this study, RINm5F cells and isolated pancreatic islets were challenged with oxidants (H2O2 or xanthine and xanthine oxidase) and incubated with conjugates (Hb-Hb or Hb-SOD-CAT) in normoxia (21% oxygen) or hypoxia (6% or 1% oxygen). Hemoglobin protection, intracellular free radical activity and cell viability in RINm5F cells measured by methemoglobin, DCF-DA and MTT assay respectively showed that cells were better protected by conjugates containing antioxidant enzymes. Insulin secretion from islets and qualitative confocal evaluation of viability showed beta cells were protected by conjugates containing antioxidant enzymes when exposed to induced stress. Our study suggested that antioxidant enzymes play a significant role in hemoglobin protection and thus extended cell protection.
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