Indeed GSTP mRNA appears to

Indeed GSTP1-1 mRNA appears to be already highly stable in K562 leukemia blue nitro with a half-live of more then 40h which is even further increasing to 92h after hemin treatment and erythroid differentiation. Previous reports quantified GST mRNA half-lives which depend on the cellular model and the expressed isoform. Benbrahim-Tallaa et al. [31] reported that the mRNA half-life time was 18h for GSTα in Sertoli cells and was unaffected by the presence of TNFα whereas FSH increased GSTα mRNA levels by increasing its mRNA stability to 119h. According to Rogiers et al. [32] the half-life of rat GSTA1/A2 mRNA in control animals was 3.6h, whereas it increased to 10.2h in phenobarbital-treated animals. Schwartz and Norris [33] demonstrated that hGSTYBX, a μ class glutathione S-transferase gene, is expressed in the DDT1MF-2 hamster smooth muscle tumor cell line. Glucocorticoid induction stabilized the corresponding mRNA with a half-life of more than 48h. Finally Jhaveri et al. reported higher GSTP1-1 mRNA stability in ER − HS578T cells compared to ER + MCF7 breast cancer cells [34]. Our results add GSTP1-1 mRNA to the erythroid-specific genes which are stabilized at the onset of differentiation. Stabilization of this mRNA during erythroid maturation raises curiosity about the potential detoxifying role of GSTP1-1 in mature erythrocytes which is the major GST isoform expressed by these cells [35]. Another example of mRNA stabilization by hemin was observed in the case of globin mRNA [36]. Moreover, during hemin-mediated erythroid differentiation of K562 cells, heat shock protein (HSP) 70 upregulation [37] was observed. Furthermore, Pirkkala et al. [38] demonstrated a multistep regulatory process of heat shock transcription factor (HSF) 2 gene expression. Indeed the increase in HSF2 protein levels is preceded by transcriptional induction of the HSF2 gene, accompanied by increased HSF2 mRNA stability after hemin-induced erythroid differentiation. This increase leads to an induced HSF-HSP interaction. Our results show that GSTP1-1 involved in oxidative stress response and detoxification against free radicals is also induced by hemin at both mRNA and protein levels and thus add GST to the enzymes involved in cellular protection during differentiation. Other inducers of erythroid differentiation were previously described to regulate specific genes at the post-transcriptional level. Formerly obtained results reported that doxorubicin induced an increased stability of PBGD and GATA-1 mRNAs, whereas aclarubicin did not affect the half-lives of these mRNAs [39]. The same author provided evidence that GTP treatment led to a drastic increase of the γ-globin mRNA half-life. This stabilizing effect of GTP was mediated via the 3′-untranslated region (UTR) of the γ-globin mRNA. In this cellular model, an early activation of γ-globin gene transcription was followed by a stabilization of its mRNA [40]. Molecular determinants of increased mRNA stability were previously described for chénaisselected erythroid specific genes including the human globin mRNA [36], [41], 15-lipoxygenase (LOX) [42] as well as the 5-aminolevulinate synthetase (eALAS) mRNA which was shown to be sufficient to confer translational control to a reporter mRNA both in transfected MEL cells and in vitro [43]. γ-Glutamyltransferase, another enzyme of the glutathione pathway was previously described to be regulated at the post-transcriptional level [44], [45]. The 3′ UTR of GSTP1-1 encompasses 76 nucleotides including a 13 nt long pyrimidine-rich region. A similar region is involved in the regulation of α-globin mRNA stabilization by (PolyC) binding protein αCP [46]. Whether this type of sequence regulates the increased stability of the GSTP1-1 mRNA remains to be elucidated. Chenais et al. [47] recently suggested that oxidative stress, generated by differentiating agents including aclarubicin, doxorubicin and butyric acid, is involved in the first step of differentiation of K562 cells towards the erythroid lineage. Hemin was also previously shown to be inducing oxidative stress in rat liver [48] which could explain the induction of the GSTP1-1 gene at the onset of the differentiation process.