L-Mimosine

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Background

L-mimosine is a prolyl 4-hydroxylase inhibitor and acts as an iron chelator [1]. In rats, it interfered with the reconstitution of the active human prolyl 4-hydroxylase with an IC50 value of 120 µM [2].Prolyl 4-hydroxylase (EC 1.14.11.2) is an α2β2 tetramer. It catalyses the formation of 4-hydroxyproline in coliagen via the hydroxylation of proline residues in the peptide linkage [3]. Prolyl-4-hydroxylase domain-containing protein (PHD) regulates HIF-1α levels in renal medulla and participates in controlling renal Na+ excretion [4].L-mimosine acted as an inhibitor for prolyl 4-hydroxylase in cultured vascular cells. L-mimosine dose-dependently inhibited the activity of prolyl hydroxylase in rat and human smooth muscle cells (SMC) and at concentrations of 400-500 µM decreased hydroxyprolyl generation by 80-90%. At that concentration, [3H]proline incorporation was decreased by < 20% in human SMC and was increased by 20% in rat SMC. These results indicated that L-mimosine quite specifically inhibited prolyl hydroxylation [2]. In rats, the pretreatment with L-mimosine for 2 weeks significantly reduced the PHD activity in kidneys. This inhibition was greater in renal medulla than in renal cortex. Western blot analysis data demonstrated that L-mimosine significantly increased protein levels of HIF-1α in the kidneys from L-mimosine-treated rats, compared with vehicle-treated rats. In animals, the pretreatment with L-mimosine substantially increased HIF-1α levels in medulla and renal cortex, but the effect in the medulla was much greater than that in the cortex. Inhibitory effects on PHD activity and HIF-1α decoyed on HIF-1α transcriptional activities in renal medulla [4]

[1]. Chung LC, Tsui KH, Feng TH, et al. L-Mimosine blocks cell proliferation via upregulation of B-cell translocation gene 2 and N-myc downstream regulated gene 1 in prostate carcinoma cells. American Journal of Physiology-Cell Physiology, 2012, 302(4): C676-C685.
[2]. McCaffrey TA, Pomerantz KB, Sanborn TA, et al. Specific inhibition of eIF-5A and collagen hydroxylation by a single agent. Antiproliferative and fibrosuppressive effects on smooth muscle cells from human coronary arteries. Journal of Clinical Investigation, 1995, 95(2): 446.
[3]. Pihlajaniemi T, Helaakoski T, Tasanen K, et al. Molecular cloning of the beta-subunit of human prolyl 4-hydroxylase. This subunit and protein disulphide isomerase are products of the same gene. The EMBO Journal, 1987, 6(3): 643.
[4]. Li N, Yi F, Sundy CM, et al. Expression and actions of HIF prolyl-4-hydroxylase in the rat kidneys. American Journal of Physiology-Renal Physiology, 2007, 292(1): F207-F216.