Role of catalase in monocytic differentiation of U937 cells by TPA: hydrogen peroxide as a second messenger

Abstract

Human promonocytic cell line U937 cells can be induced to differentiate into macrophages by treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA treatment induced the expression of the monocytic differentiation markers CD11b and CD36, with concomitant morphological changes. Moreover, TPA enhanced reactive oxygen species (ROS) generation in these cells, and phagocytic ability was also stimulated during differentiation. The antioxidant agent N-acetyl-L-cysteine inhibited the TPA-induced differentiation of U937 cells. TPA treatment decreased the expression level of catalase, which catalyzes the decomposition of hydrogen peroxide (H 2 O 2 ) to H 2 O and O 2 . In contrast, TPA increased the level of manganese superoxide dismutase, which catalyzes the dismutation of superoxide into H 2 O 2 and O 2 without affecting the levels of copper-zinc superoxide dismutase or glutathione peroxidase 1, which removes H 2 O 2 using glutathione as substrate. Treatment of U937 cells with catalase inhibited the enhancement of ROS generation induced by TPA, and blocked the TPA-induced differentiation of U937 cells. Human promyelocytic cell line HL60 cells were also induced to differentiate into macrophages by TPA. However, HP100-1 cells, its variant cell line overexpressing catalase, were resistant to TPA-induced differentiation. Our results suggest that catalase inhibits monocytic differentiation by TPA; the decrease in catalase level and the accumulation of H 2 O 2 are significant events for monocyte/ macrophage differentiation by TPA.

CoCl₂ Decreases EC-SOD Expression through Histone Deacetylation in COS7 Cells

“…14) Recent studies reported that epigenetics, such as DNA methylation and histone modifications, play pivotal roles in the progression of CKD, and some inhibitors of histone deacetylase (HDAC) exert beneficial effects against CKD. [15][16][17] Moreover, the expression of EC-SOD is known to be regulated by epigenetics in human lung cancer cells, 18,19) monocytes/macrophages, 20) and retina endothelial cells 21) ; however, limited information is currently available on EC-SOD regulation mechanisms in CKD models and the involvement of epigenetics.…”

p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation

“…Nevertheless, there are almost no studies addressing this issue, with just one report describing the differentiation of a promonocytic cell line into macrophages. 12 Moreover, to our knowledge, there are no reports exploring the possible role of ROS and NADPH oxidases in the differentiation of HSCs or in other haematopoietic lineages other than macrophages, including megakaryocytic differentiation, that is, the process of maturation of megakaryocytes from HSCs that releases circulating platelets. 13 K562 and HEL cells are commonly used to study different aspects related to megakaryocytopoiesis because they undergo megakaryocytic differentiation in response to phorbol esters.…”

La voie Nrf2 en pathologie respiratoire

“…De nombreuses études ont montré l'importance du stress oxydant et sa participation à la physiopathologie de la fibrose pulmonaire [4]. On sait que les ROS sont des modulateurs de la différenciation cellulaire [2]. L'expression de la NOX4/NADPH oxydase à l'origine d'une augmentation des ROS est augmentée dans les fibroblastes pulmonaires de patients atteints de FPI [22].…”

“…En effet, ROS et RNS sont largement impliquées dans les réponses cellulaires physiologiques telles que les défenses anti-infectieuses, les voies de signalisation intracellulaires et la réponse mitogène. Les ROS sont des éléments modulateurs des états d'activation et de différenciation cellulaires [2,3] par l'intermédiaire des kinases/phosphatases et de leurs seconds messagers. Les ROS sont également capables de promouvoir la croissance cellulaire voire de favoriser un phénotype cancéreux, ou, à l'inverse, d'induire la sénescence et l'apoptose [4][5][6][7].…”