The Effect of the Copper Chelator Tetraethylenepentamine on Reactive Oxygen Species Generation by Human Hematopoietic Progenitor Cells

2007 ◽  
Vol 16 (6) ◽  
pp. 1053-1056 ◽  
Author(s):  
Eugenia Prus ◽  
Eitan Fibach
Blood ◽  
2010 ◽  
Vol 115 (6) ◽  
pp. 1238-1246 ◽  
Author(s):  
Paul S. Hole ◽  
Lorna Pearn ◽  
Amanda J. Tonks ◽  
Philip E. James ◽  
Alan K. Burnett ◽  
...  

Abstract Excessive production of reactive oxygen species (ROS) is a feature of human malignancy and is often triggered by activation of oncogenes such as activated Ras. ROS act as second messengers and can influence a variety of cellular process including growth factor responses and cell survival. We have examined the contribution of ROS production to the effects of N-RasG12D and H-RasG12V on normal human CD34+ progenitor cells. Activated Ras strongly up-regulated the production of both superoxide and hydrogen peroxide through the stimulation of NADPH oxidase (NOX) activity, without affecting the expression of endogenous antioxidants or the production of mitochondrially derived ROS. Activated Ras also promoted both the survival and the growth factor–independent proliferation of CD34+ cells. Using oxidase inhibitors and antioxidants, we found that excessive ROS production by these cells did not contribute to their enhanced survival; rather, ROS promoted their growth factor–independent proliferation. Although Ras-induced ROS production specifically activated the p38MAPK oxidative stress response, this failed to induce expression of the cell-cycle inhibitor, p16INK4A; instead, ROS promoted the expression of D cyclins. These data are the first to show that excessive ROS production in the context of oncogene activation can promote proliferative responses in normal human hematopoietic progenitor cells.


Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 419-428 ◽  
Author(s):  
Melania Tesio ◽  
Karin Golan ◽  
Simona Corso ◽  
Silvia Giordano ◽  
Amir Schajnovitz ◽  
...  

Abstract Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor–induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell–derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and c-Met activation. We found that c-Met inhibition reduced mobilization of both immature progenitors and the more primitive Sca-1+/c-Kit+/Lin− cells and interfered with their enhanced chemotactic migration to stromal cell–derived factor 1. c-Met activation resulted in cellular accumulation of reactive oxygen species by mammalian target of rapamycin inhibition of Forkhead Box, subclass O3a. Blockage of mammalian target of rapamycin inhibition or reactive oxygen species signaling impaired c-Met–mediated mobilization. Our data show dynamic c-Met expression and function in the bone marrow and show that enhanced c-Met signaling is crucial to facilitate stress-induced mobilization of progenitor cells as part of host defense and repair mechanisms.


The eff ect of the non-opiate analog of leu-enkephalin (peptide NALE: Phe – D – Ala – Gly – Phe – Leu – Arg) on the reactive oxygen species generation in the heart of albino rats in the early postnatal period was studied. Peptide NALE was administered intraperitoneally in the dose of 100 μ/kg daily from 2 to 6 days of life. Reactive oxygen species generation was assessed by chemiluminescence in the heart homogenates of 7-day-old animals. Decreasing of reactive oxygen species generation nearly by 30 % and an increasing in antioxidant system activity by the 20-27 %, compared with the control parameters, were found. The antioxidant eff ect of peptide NALE is associated with the presence of the amino acid Arg in the structure of the peptide. An analogue of NALE peptide, devoid of Arg (peptide Phe – D – Ala – Gly – Phe – Leu – Gly), had a signifi cant lower antioxidant eff ect. The NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the dose 50 mg/kg, administered with NALE peptide, reduced the severity of the NALE antioxidant eff ect. The results of the study suggest that the pronounced antioxidant eff ect of NALE peptide in the heart of albino rats, at least in part, is due to the interaction with the nitric oxide system.


1993 ◽  
Vol 149 (1) ◽  
pp. 64-67 ◽  
Author(s):  
Donald L. Weese ◽  
Michael L. Peaster ◽  
Kyle K. Himsl ◽  
Gary E. Leach ◽  
Pramod M. Lad ◽  
...  

2020 ◽  
Vol 21 (14) ◽  
pp. 4970
Author(s):  
Juan Perdomo ◽  
Carlos Quintana ◽  
Ignacio González ◽  
Inmaculada Hernández ◽  
Sara Rubio ◽  
...  

Melatonin is present in all living organisms where it displays a diversity of physiological functions. Attenuation of melanogenesis by melatonin has been reported in some mammals and also in rodent melanoma cells. However, melatonin may also stimulate melanogenesis in human melanoma cells through mechanisms that have not yet been revealed. Using the human melanoma cells SK-MEL-1 as a model, an increase in both tyrosinase activity and melanin was already observed at 24 h after melatonin treatment with maximal levels of both being detected at 72 h. This effect was associated with the induction in the expression of the enzymes involved in the synthesis of melanin. In this scenario, glycogen synthase kinase-3β seems to play a significant function since melatonin decreased its phosphorylation and preincubation with specific inhibitors of this protein kinase (lithium or BIO) reduced the expression and activity of tyrosinase. Blocking of PI3K/AKT pathway stimulated melanogenesis and the effect was suppressed by the inhibitors of glycogen synthase kinase-3β. Although melatonin is a recognized antioxidant, we found that it stimulates reactive oxygen species generation in SK-MEL-1 cells. These chemical species seem to be an important signal in activating the melanogenic process since the antioxidants N-acetyl-l-cysteine and glutathione decreased both the level and activity of tyrosinase stimulated by melatonin. Our results support the view that regulation of melanogenesis involves a cross-talk between several signaling pathways.


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