Barthi et al previously showed

Barthi et al.[43] previously showed that curcumin inhibits IKK complex activity and thus IκBα phosphorylation as well as the p65 nuclear translocation. Those data are in agreement with our results obtained by gel shift assays using GSTP1-1 promoter and consensus NF-κB probes. Moreover, luciferase activities generated by constructs associating GSTP1-1 promoter fragments of increasing length to a luciferase reporter gene were strongly inhibited by curcumin as was a similar construct harbouring five NF-κB repeats. In 1995, Singh and Aggarwal [18] using a ML-1a myelomonoblastic leukemia cell line showed that curcumin inhibits AP-1 binding onto a consensus AP-1 site. These results are in agreement with our data, where curcumin strongly inhibits TNFα- and TPA-induced bindings onto GSTP1-1 and consensus AP-1 probes. Inhibition of both NF-κB and AP-1 bindings thus accounts for the observed transcriptional inhibition. Moreover, Gilot et al.[50] noticed that overexpression of ASK-1 restored caspase-3 activation and apoptosis in primary cultures of hepatocytes. Co-transfections of GSTM1/2, GSTA1/2 or GSTP1-1 isoforms with ASK-1 reduced apoptosis by antagonising ASK-1 activity and thus demonstrating the antiapoptotic function of the GSTs.
Acknowledgements
Glutathione -transferases (GST, EC.2.5.1.18) represent an extended family of phase II detoxification p2x receptors expressed in animals and plants and found mainly in the cytosol . The major role of these enzymes is to catalyze the conjugation of glutathione to a wide variety of exogenous electrophilic substrates including anticancer drugs, toxins, pesticides, and genotoxic molecules, allowing compounds to be exported from the cell through the GS-X pump in an ATP-dependent manner . Enzymes of the mammalian GST family are classified into eight cytosolic and one microsomal isoform . The human pi class of GST, GSTP1-1, is expressed in most human tissues specifically in placenta and red cells but not in adult liver and in cancer cell lines like the Burkitt lymphoma Raji, HepG2 hepatoma, and MCF7 breast cancer cells . Moreover, GSTP1-1 expression is regulated during the cell cycle with the highest amount expressed in G2 and S phases . High levels of GSTP1-1 are observed in proliferating fetal tissues and mature epithelia , . However, increased expression levels of GSTP1-1 are associated with malignant transformation and tumor development of a wide range of tissues , , , , . In many human tumors and preneoplasic lesions, the GSTP1-1 protein is overexpressed even though in the corresponding normal tissues it is either absent or expressed at very low levels . GSTP1-1, a useful tumor marker , is also involved in resistance against antineoplastic drugs and genotoxic carcinogens , . The human pluripotent chronic myelogenous leukemia cell line K562 is capable of undergoing differentiation along lineage specific pathways in response to a variety of agents like 12--tetradecanoyl phorbol 13-acetate (TPA) or anthracyclines providing an ideal model to study the regulation of GSTP1-1 during differentiation. GATA-1 and -2 are zinc-finger transcription factors which bind to the consensus (T/A)GATA(A/G) binding motif identified in regulatory sequences of erythroid and megakaryocytic specific genes , , , . These transcription factors are involved in differentiation, proliferation, and terminal maturation of multipotent hematopoietic stem cells and progenitors towards the erythroid and megakaryocytic lineages .
Although incidence rates of and mortality due to heart failure (HF) as a common and often fatal complication of myocardial infarction (MI) have decreased over the past 3 decades, HF has still a poor absolute survival., Other studies indicate an increase in prevalence of HF with preserved ejection fraction, although the mortality rate from the disorder remains unchanged. Preventing MI-induced HF is therefore highly desirable.