Research Article: Alpha 1 Microglobulin: A Potentially Paradoxical Anti-Oxidant Agent

Date Published: September 25, 2017


Author(s): Richard A Zager.


Alpha 1 microglobulin is a low molecular weight heme binding antioxidant protein with interesting, and potentially important, clinical applications. However, much remains to be learned about its in vivo effects. This invited review raises a number of physiologic issues regarding this compound as it pertains to clinical use.

Partial Text

Alpha 1 microglobulin (A1M) is a small globular plasma protein that is universally present in vertebrates, including humans. It is predominantly synthesized in liver and then gains systemic distribution following hepatic release. Its function is that of a potent free heme binder (second only in avidity to hemopexin) and as an antioxidant protein [1-5]. As such, there has been considerable interest in the use of recombinant A1M (rAIM) as an anti-oxidant agent, particularly in settings in which free heme or heme proteins are released into the circulation (e.g. traumatic myohemoglobinuria, intravascular hemolysis and pre-eclampsia). Given its small size (∼26 kDa; 183 amino acids), A1M is readily filtered by the renal glomerulus. Upon delivery into tubular lumina, it is largely reabsorbed by proximal tubules, presumably via the megalin-cubulin pathway [2]. Because the proximal tubule is the primary target of ischemic and nephrotoxic injuries, and because oxidant stress is evoked in virtually of forms of renal damage [6], rA1M therapy has been proposed as a renal therapeutic with potential broad based clinical application, e.g. pre-eclampsia, toxic and ischemic acute kidney injury, and chronic renal disorders such as diabetic nephropathy.

It should be recalled that in the pharmacologic sciences, an initially expected protective action of a particular agent may occur, but upon subsequent investigations, unanticipated protective mechanisms are shown to be involved. In light of the above considerations, perhaps the same might be true of A1M. These possibilities seemingly deserve consideration as clinical trials with rA1M are soon to commence.




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