Hydroquinone modulates the GM-CSF signaling pathway in TF-1 cells

Abstract

Human leukemogens, including alkylating chemotherapeutic agents and benzene, enhance granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent proliferation of human CD34 þ bone marrow (BM) cells. The extracellular signal-regulated kinase (ERK) pathway plays an important role in GM-CSF-dependent proliferation and also has been implicated in the pathogenesis of acute myelogenous leukemia. Therefore, we investigated the effects of the benzene metabolite, hydroquinone (HQ), on alterations in the GM-CSF signaling pathway in TF-1 erythroleukemia cells and human CD34 þ BM cells. HQ treatment in TF-1 cells results in a strong proliferative response that is dependent on ERK activation and GM-CSF production. HQ also induces ERK-dependent AP-1 activation with concomitant increased transcriptional activity of AP-1 reporter gene. However, the kinetics of ERK activation are different between rhGM-CSF and HQ in TF-1 cells: rhGM-CSF results in immediate activation of ERK, whereas HQ activation of ERK is delayed. Further, HQ and rhGM-CSF together produce an immediate increase in ERK phosphorylation, which is sustained for over 48 h. HQ also stimulates colony formation, AP-1 DNA binding and GM-CSF production in human CD34 þ BM cells. These results suggest that HQ stimulates proliferation via activation of ERK/AP-1 and is at least partially mediated via the production of GM-CSF.

Benzene Metabolite Hydroquinone Up-Regulates Chondromodulin-I and Inhibits Tube Formation in Human Bone Marrow Endothelial Cells

“…The ChM-I core promoter region contains an AP-1 binding site (Yanagihara et al, 2000), and hydroquinone has been reported to enhance AP-1 activation in TF-1 erythroleukemia cells (Zheng et al, 2004). Whether hydroquinone can up-regulate ChM-I via AP-1 activation needs further investigation.…”

Systematic literature review on Parkinson's disease and Childhood Leukaemia and mode of actions for pesticides

“…Activation of MAP kinases such as ERK, p38 and JNK has been reported Ruiz-Ramos et al, 2005;Zheng et al, 2004a). It has been suggested that 1,4-BQ-induced ROS production leads to the activation of ERK signalling pathway, leading to increased proliferation of leukaemic cells .…”

“…Also, HQ can stimulate proliferation and colony formation of human bone marrow progenitor (i.e. CD34+) cells by activation of ERK/AP-1 pathway (Zheng et al, 2004a).…”

Effects Of Benzene on Human Hematopoiesis

“…Hydroquinone enhances cytokine-dependent clonal proliferation of a subpopulation of human CD34 + BM cells, which appears to be mediated via the extracellular signal-regulated kinase/activation protein-1 signaling pathway [133][134][135][136]. Hydroquinone has also been reported to synergize with tumor necrosis factor to induce apoptosis in human CD34 + hematopoietic progenitor cells by inhibiting nuclear factorkappa B [137], and to inhibit macrophage-mediated immune responses by modulating intracellular signaling and protective mechanisms [138].…”