The peroxidatic activities of Myoglobin and Hemoglobin, their pathological consequences and possible medical interventions.
The peroxidatic activities of Myoglobin and Hemoglobin, their pathological consequences and possible medical interventions.
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DOI：
10.1016/j.mam.2021.101045
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发表时间：
2022-04
影响因子：
10.6
通讯作者：
Reeder BJ
中科院分区：
文献类型：
--
作者：
Wilson MT;Reeder BJ
在肌红蛋白和血红蛋白逃离细胞环境，从而脱离细胞还原/保护系统的病理条件下，这些蛋白固有的过氧化物酶活性可以表达出来。这种活性导致了高氧化性的氧基铁物种的形成。这在体内发生的证据是通过在血红素基团和蛋白质之间形成共价键来提供的，这是一个明确的生物标志物，表明存在氧合铁形式。过氧化活性还会导致脂类的氧化，其产物可能是强大的血管收缩药(如异前列腺素、神经前列腺素)。在这里，我们回顾了横纹肌溶解和蛛网膜下腔出血后发生脂质氧化的证据，以及磷脂的花生四烯酸链形成的产物通过血管收缩导致肾功能衰竭和脑血管痉挛的证据。对这些病理条件的干预通过给予还原剂来去除铁基血红素进行了讨论。通过蛋白质的电子转移途径，促进铁基还原在低浓度的还原剂已被确定。最后，我们考虑了以血红蛋白为基础的氧气载体的治疗用途，以及如何通过设计这种电子转移途径将其转化为血红蛋白来降低这些载体的毒性。
Under those pathological conditions in which Myoglobin and Hemoglobin escape their cellular environments and are thus separated from cellular reductive/protective systems, the inherent peroxidase activities of these proteins can be expressed. This activity leads to the formation of the highly oxidizing oxo-ferryl species. Evidence that this happens in vivo is provided by the formation of a covalent bond between the heme group and the protein and this acts as an unambiguous biomarker for the presence of the oxo ferryl form. The peroxidatic activity also leads to the oxidation of lipids, the products of which can be powerful vasoconstrictive agents (e.g. isoprostanes, neuroprostanes). Here we review the evidence that lipid oxidation occurs following rhabdomyolysis and sub-arachnoid hemorrhage and that the products formed from arachidonic acid chains of phospholipids lead, through vasoconstriction, to kidney failure and brain vasospasm. Intervention in these pathological conditions through administration of reducing agents to remove ferryl heme is discussed. Through-protein electron transfer pathways that facilitate ferryl reduction at low reductant concentration have been identified. We conclude with consideration of the therapeutic use of Hemoglobin Based Oxygen carriers and how the toxicity of these may be reduced by engineering such electron transfer pathways into hemoglobin.
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影响因子：
6.6
作者：
Corcoran, Tomas B.;Mas, Emilie;Mori, Trevor A.
通讯作者：
Mori, Trevor A.
影响因子：
7.4
作者：
Hsieh, Yu-Ping;Lin, Chih-Lung;Yen, Hsiu-Chuan
通讯作者：
Yen, Hsiu-Chuan
DOI：
10.1177/096032718300200204
发表时间：
1983-01-01
期刊：
HUMAN TOXICOLOGY
影响因子：
--
作者：
HAMPEL, G;HORSTKOTTE, H;RUMPF, KW
通讯作者：
RUMPF, KW
DOI：
10.3891/acta.chem.scand.02-0264
发表时间：
1948-01-01
期刊：
ACTA CHEMICA SCANDINAVICA
影响因子：
--
作者：
DEDUVE, C
通讯作者：
DEDUVE, C
影响因子：
11.4
作者：
Chakane S;Matos T;Kettisen K;Bulow L
通讯作者：
Bulow L