Hemin chloride

Hemin chloride is an oxidized form of heme that inhibits eukaryotic translation initiation factor 2α kinase 1 (eIF2αK1), a repressor of eIF-2α [1].

The eukaryotic initiation factor 1 (eIF1) plays an important role in translation start site specificity. The eIF2α is a key target in translational regulation. Phosphorylation of eIF2α on Ser51 converts eIF2 from a substrate to a competitive inhibitor of its exchange factor, eIF2β[2].

In vitro: The addition of hemin (30 μM) depressed the extent of incorporation of phosphate into eIF-2β by about 50% [1]. Concentrations of 25 μM hemin significantly decreased the rate of incorporation of phosphate into eIF-2α. Concentrations of hemin ranged from 20 to 40 μM maintained an optimal rate of protein synthesis in cell lysates [1].

In vivo: In mice, pretreated with an intraperitoneal injection of hemin displayed a marked induction of HO-1. In hemin-treated mice, thrombus formation was delayed, and the delay was completely blunted by tin protoporphyrin-IX [3].

References:

[1] Tahara S M, Traugh J A, Sharp S B, et al. Effect of hemin on site-specific phosphorylation of eukaryotic initiation factor 2[J]. Proceedings of the National Academy of Sciences, 1978, 75(2): 789-793.[]

[2] Sonenberg N, Dever T E. Eukaryotic translation initiation factors and regulators[J]. Current opinion in structural biology, 2003, 13(1): 56-63.

[3] Lindenblatt N, Bordel R, Schareck W, et al. Vascular heme oxygenase-1 induction suppresses microvascular thrombus formation in vivo[J]. Arteriosclerosis, thrombosis, and vascular biology, 2004, 24(3): 601-606