Hemin

Hemin, a physiological erythroid maturation stimulator, is able to induce the expression of critical autophagic genes (Map1a1b (LC3), Beclin-1 gen, Atg5) in an erythroleukemia cell type; increases the size of autophagic vacuoles and induces mitophagy in K562 cells; a heme oxygenase (HO) 1 inducer. (In Vitro) :Hemin and PGJ2, used as positive controls, strongly increase both expression and activity of HMOX after 4 and 12 h, respectively. Indeed, a significant effect is found of 30 μM Hemin on cell proliferation in all used cell lines after 48 h, which is dose-dependent. Hemin treatment decreases cell proliferation to 62±5 %, 51±3 %, and 38±8 % in PA-TU-8902, BxPC-3 and MiaPaCa-2 cancer cells, respectively, with p<0.0001 for all comparisons. Furthermore, enhancement of anti-proliferative effects of statins is observed by Hemin, documented as decreased cell proliferation after 48 h of co-treatment. (In Vivo) :Following the i.p. administration of Hemin (100 μmol/kg), the HO-1 level in the renal cortex begins to increase gradually. The HO-1 level reaches its peak 24 h after Hemin preconditioning. HO-1 is expressed mainly in the renal tubules. The HO-2 level in the kidney does not change following Hemin preconditioning.