ASSESSMENT OF HEMOGLOBIN-DEPENDENT NEUROTOXICITY - ALPHA-ALPHA CROSS-LINKED HEMOGLOBIN

被引:17
|
作者
PANTER, SS [1 ]
VANDEGRIFF, KD [1 ]
YAN, PO [1 ]
REGAN, RF [1 ]
机构
[1] LETTERMAN USA HOSP, REG VET LAB, SAN FRANCISCO, CA 94129 USA
关键词
D O I
10.3109/10731199409117870
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Adult human hemoglobin A(0) (HbA(0)) has been shown to be neurotoxic, and we wish to report on similar studies conducted using a modified hemoglobin, which has been crosslinked between the alpha subunits (alpha-alpha Hb). Cortical cell cultures were prepared from fetal Swiss-Webster mice at 15-16 days gestation. Mature cultures (days in vitro, 12-16) were exposed to alpha-alpha Hb in a defined medium for 24-48 hours at 37 degrees C. Low micromolar amounts of alpha-alpha Hb were neurotoxic in a concentration-dependent fashion. This toxicity was attenuated by the antioxidants Trolox and U-74500A and by the iron chelator deferoxamine. The hemoglobin-binding protein, haptoglobin, also completely blocked alpha-alpha Hb-dependent neurotoxicity. The latter result was unexpected because complex formation between alpha-alpha-Hb and haptoglobin was not detected using assays of haptoglobin fluorescence and hemoglobin peroxidase activity.
引用
收藏
页码:399 / 413
页数:15
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