Up-regulation of α1-microglobulin by hemoglobin and reactive oxygen species in hepatoma and blood cell lines

A1M, an extravascular tissue cleaning and housekeeping protein

“…Up-regulated expression of A1M, both on mRNA-and protein levels, has been shown in human cell lines, primary keratinocytes, and skin and retinas explants after exposure to stress-conditions with hydrogen peroxide, hydroxyl radicals, Hb and heme [32,53,54]. This is supported by human in vivo data.…”

Perfusion of human placenta with hemoglobin introduces preeclampsia-like injuries that are prevented by α1-microglobulin

“…An A1M concentration of 22 μM, corresponding to a tenfold excess of Hb, visavi A1M, was chosen because, as mentioned above, A1M does not interact with Hb itself but rather with free heme and radicals expected to be generated at a much lower steady-state concentration. In addition, the radical-scavenging capacity of A1M was shown to be approximately 8-9 radicals / A1M-molecule [24]. It has also been shown previously that a molar deficit of A1M is sufficient to protect cultured cells against oxidation by an excess of Hb or free heme [20].…”

“…Recent reports have shown that A1M is a heme-and radical-scavenger, involved in the defense against oxidative stress induced by free Hb and participating in the degradation of heme [18,19,23]. Its synthesis is up-regulated, both in liver and peripheral cells, as a consequence of elevated concentrations of free Hb, heme and ROS [24].…”

Vitreous levels of oxidative stress biomarkers and the radical-scavenger α1-microglobulin/A1M in human rhegmatogenous retinal detachment

“…Oxidative stress-induced A1M upregulation has also been shown in several tissues including liver, blood cell lines [16], keratinocyte primary cultures, and skin explants [4]. In the eye, A1M upregulation could theoretically be derived from a disturbed blood-ocular barrier function and/or local upregulation in eye tissues.…”

“…In addition, an increased synthesis in liver, blood cells, placenta and skin keratinocytes is induced by cell-free Hb and ROS [4,5,16].…”