A Review of the Action of Magnesium on Several Processes Involved in the Modulation of Hematopoiesis

Abstract

Magnesium (Mg²⁺) is an essential mineral for the functioning and maintenance of the body. Disturbances in Mg²⁺ intracellular homeostasis result in cell-membrane modification, an increase in oxidative stress, alteration in the proliferation mechanism, differentiation, and apoptosis. Mg²⁺ deficiency often results in inflammation, with activation of inflammatory pathways and increased production of proinflammatory cytokines by immune cells. Immune cells and others that make up the blood system are from hematopoietic tissue in the bone marrow. The hematopoietic tissue is a tissue with high indices of renovation, and Mg²⁺ has a pivotal role in the cell replication process, as well as DNA and RNA synthesis. However, the impact of the intra- and extracellular disturbance of Mg²⁺ homeostasis on the hematopoietic tissue is little explored. This review deals specifically with the physiological requirements of Mg²⁺ on hematopoiesis, showing various studies related to the physiological requirements and the effects of deficiency or excess of this mineral on the hematopoiesis regulation, as well as on the specific process of erythropoiesis, granulopoiesis, lymphopoiesis, and thrombopoiesis. The literature selected includes studies in vitro, in animal models, and in humans, giving details about the impact that alterations of Mg²⁺ homeostasis can have on hematopoietic cells and hematopoietic tissue.

Keywords: bone marrow; hematopoietic cells; hematopoietic tissue; immune cells; magnesium.

Figure 1

On the hematopoietic cell surface, transient receptor potential cation channel subfamily M member 7 (TRPM7) and magnesium transporter 1(MagT1) facilitate magnesium influx into the cell. In the cytoplasm, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is magnesium-sensitive, and the activation of this signaling cascade induces cell growth, proliferation, and the inhibition of autophagy. Additionally, increased Mg²⁺ concentration is able to decrease proinflammatory cytokine production, by inhibiting the nuclear translocation and phosphorylation of nuclear factor kappa B (NF-κB) and rise in basal inhibitor of NF-κB (IĸBα) levels, downregulating tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β release, and reducing ROS production. Solid black arrows indicate the pathway activated, while dot black arrows indicate the pathways inhibited. Red arrows pointing down indicates reduction, while blue arrows pointing up indicates increase.