Oxidative damage and cell cycle delay induced by vanadium(III) in human peripheral blood cells.

Vanadium (V) is a metal that can enter the environment through natural routes or anthropogenic activity. In the atmosphere, V is present as V oxides, among which vanadium(III) oxide (V2O3) stands out. Cytogenetic studies have shown that V2O3 is genotoxic and cytostatic and induces DNA damage; however, the molecular mechanisms leading to these effects have not been fully explored. Therefore, we treated human peripheral blood lymphocytes in vitro, evaluated the effects of V2O3 on the phases of the cell cycle and the expression of molecules that control the cell cycle and examined DNA damage and the induction of oxidative stress. The results revealed that V2O3 did not affect cell viability at the different concentrations (2, 4, 8 or 16 µg/mL) or exposure times (24 h) used. However, V2O3 affected the percentage of G1- and S-phase cells in the cell cycle, decreased the expression of mRNAs encoding related proteins (cyclin D, cyclin E, CDK2 and CDK4) and increased the expression of γH2AX and the levels of reactive oxygen species. The ability of V2O3 to cause a cell cycle delay in G1-S phase may be associated with a decrease in the mRNA and protein expression of the cyclins/CDKs and with intracellular oxidative stress, which may cause DNA double-strand damage and H2AX phosphorylation.

Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model.

Acute myeloid leukaemia results from the neoplastic transformation of haematopoietic stem cells. Although advances have been made in its treatment, the mortality rate remains high. As a result, therapeutic alternatives continue to be explored. In this study, we present evidence that suggests that casein, the principal protein in milk, possesses significant antileukaemic properties. We investigated whether casein inhibited the in vitro proliferation and induced the apoptosis of the mouse myelomonocytic leukaemia cell line WEHI-3. By contrast, under identical conditions, casein markedly promotes the proliferation of mouse normal mononuclear bone marrow cells. Since the selective elimination of leukaemia cells is an ideal therapeutic strategy, we also evaluated the antileukaemic potential of casein in vivo. The results showed that casein increases the survival of mice bearing WEHI-3-induced tumours, suggesting that this molecule is also capable of inhibiting the proliferation of these cells in vivo. The evidence that casein inhibited cell proliferation and induced apoptosis in leukaemia cells in vitro, but increased survival in vivo in a leukaemia mouse model, indicates that casein may be useful in leukaemia therapy.

Tai chi diminishes oxidative stress in Mexican older adults.

OBJECTIVE: To determine the effect of Tai Chi on oxidative stress in a population of elderly Mexican subjects. DESIGN: It was carried out a quasi-experimental study with a sample of 55 healthy subjects randomly divided into two age-matched groups: (i) a control group with 23 subjects and (ii) an experimental group with 32 subjects. The experimental group received daily training in Tai Chi for 50 min. MEASUREMENTS: It was measured before and after 6-month of exercise period: thiobarbituric acid reactive substances (TBARS), total antioxidant status (TAS), superoxide dismutase (SOD), and glutathione peroxidase (GPx). RESULTS: It was found that the experimental group exhibited a statistically significant decrease in glucose levels, total cholesterol, low-density lipoprotein cholesterol (LDLC), and systolic blood pressure, as well as an increase in SOD and GPx activity and TAS compared with the control group (p < 0.05). CONCLUSIONS: Our findings suggest that the daily practice of Tai Chi is useful for reducing OxS in healthy older adults.

Sodium caseinate induces secretion of macrophage colony-stimulating factor from neutrophils.

In this work we provide evidence that granulocytes produce macrophage colony-stimulating factor (M-CSF) in the band cell stage and secrete it upon sodium caseinate-mediated differentiation to polymorphonuclear cells. We identified M-CSF in an enriched population of myeloid band cells from murine bone marrow using a chromophore-labeled monoclonal anti-M-CSF antibody. An ELISA assay was then used to detect secreted M-CSF in culture supernatants of enriched band cells differentiated to mature neutrophils using sodium caseinate. Colony formation in vitro by the supernatants from differentiating band cells was blocked by anti-M-CSF, thus suggesting that this factor is the only one responsible for this activity. Our data imply that casein can modulate hematopoiesis possibly via M-CSF production. Finally we discuss the possibility whether this M-CSF in concert with G-CSF could establish a cellular communication network between macrophages and granulocytes allowing them to simultaneously arrive at the inflammatory site.

Alpha-, beta- and kappa-caseins inhibit the proliferation of the myeloid cell lines 32D cl3 and WEHI-3 and exhibit different differentiation properties.

We have recently shown that sodium caseinate (CasNa) was able to inhibit the proliferation of the myeloid cell line 32D cl3 in a non-toxic way, and that it also induced the expression of macrophage colony-stimulating factor (M-CSF). Casein is the main protein present in milk and is composed of alpha (alpha), beta (beta) and kappa (kappa) subunits. This work was undertaken to evaluate if any one casein is responsible for the proliferation and differentiation properties found for CasNa on myeloid cells. Taking into consideration that 32D cl3 cells are considered to be non-malignant and dependent on IL-3 for proliferation, we also included for this study a leukemic cell line, WEHI-3, that does not depend on any external growth factor for its proliferation in order to evaluate if the growth inhibitory effect of caseins is also present for malignant cells. Our results showed that all caseins were inhibitory for the proliferation of either 32D cl3 and WEHI-3 and that only the 32D cl3 cells were induced to differentiate into the monocyte-macrophage lineage. In order to evaluate if CasNa was able to inhibit the proliferation of other myeloid cells we used J774 and P388 and found that they were also inhibited. We also determined that the different caseins exhibit different differentiation properties, with alpha-casein being the only one able to induce the secretion of M-CSF. We consider this work to open a new field of research, where casein, or its components, can be studied for their possible role in hematopoiesis and on the inhibition of malignant cell proliferation for therapeutic use.

[Stem cell factor (SCF) supports granulocyte progenitor survival in mouse bone marrow cultures]. / El factor de células totipotenciales (stem cell factor; SCF) sostiene la supervivencia de progenitores de granulocitos en cultivos de médula ósea de ratón.

The regulation of cell differentiation and cell death in crucial to the generation of hematopoietic cells both in vitro and in vivo. The biologic role of stem cell factor (SCF) in hematopoietic cell development is not well known. We monitored the survival, proliferation and differentiation of mouse hematopoietic cells in culture in the presence of SCF. Examination of colony formation, MTT and thymidine killing of mouse bone marrow indicated that SCF is mainly a survival factor. Our results show that SCF maintains cells in a "undifferentiated" state. Committed granulocytic and monocytic progenitors (CFU-GM) survive for seven days in the presence of SCF alone, under conditions where no maturing granulocytic monocytic cells could be recovered. On transfer to GM-CSF containing cultures, these cells proliferate and differentiate terminally. Together, our data indicate that SCF induces survival in hematopoietic progenitors. Furthermore, SCF favors the survival of granulocytic progenitors over that of monocytic progenitors. In the absence of later acting factors such as GM-CSF, cells that progress beyond the CFU-GM stage lose c-kit expression and die by default. Hence, lack of cell expansion in the presence of SCF by itself is due to constant cell proliferation and survival, which is counterbalanced by cell death. In contrast, the presence of both SCF and GM-CSF allows for the continuous survival and expansion of hematopoietic progenitor cells in culture, as well as favoring their terminal differentiation along granulocytic and monocytic pathways. Furthermore, GM-CSF induces colonies of macrophages that produce G-CSF and IL-6, two molecules involved in granulopoiesis, and these in turn stimulate granulocyte colony formation. Finally, our data suggest that survival signals by SCF are crucial during the differentiative process of granulocytes, giving strength to deterministic model.

[Biology of hematopoietic stem cells]. / Biología de las células totipotenciales hematopoyéticas.

All the cells comprising the hemopoietic system are derived from a common precursor, the totipotent hemopoietic cell (THC), which, through processes of proliferation and differentiation, gives rise to all the mature cells found in the blood and lympho-hemopoietic organs. In order that the processes of proliferation, survival, apoptosis, and differentiation from THCs to mature cells take place, the participation of proteins denoted collectively as cytokines is required. Their role is to promote and regulate one or several functions (depending on the cell type and stage of development), and to participate in one or several stages of cell development of the THCs. By the use of different tissue culture techniques, it was concluded that other non-hemopoietic cell types have an important role. These cells are those comprising the stroma in the bone marrow: fibroblasts, endothelial cells and adipocytes among others. The contribution of the stroma lies in the production of cytokines, as well as providing sustenance for the THCs. Even when it could seem that cytokines are fundamental factors in the regulation of the main functions of the hemopoietic cells, two models have been proposed to explain the process of hemopoiesis: the deterministic and the stocastic. Both models provide some evidence to support their postulates, however, to this date it is not possible, in view of the data, to decide which of the models is more accurate without incurring controversy. Even though the study of the THCs promotes a great number of questions about the basic mechanisms that regulate them, in several laboratories in the world a new aspect of research: their use in transplants, using THCs as a substitute for whole bone marrow transplant and, still in the initial stages, their use as targets for gene therapy for deficiency diseases or even for therapy against cancer.