Time-dependent effects of hypoxia on cell metabolism, signaling, and iron homeostasis in the hematopoietic progenitor model KG1a.

Lowered availability of oxygen in the micro-environment of cells perturbs metabolic and signaling pathways. It affects proliferation, tissue morphology, and differentiation. Leukemia impairs maturation of hematopoietic progenitors: the immune system, healing, and erythropoiesis are weakened, thereby perturbing iron homeostasis and further lowering oxygen provision to tissues.

Low-level cadmium doses do not jeopardize the insulin secretion pathway of β-cell models until the onset of cell death.

Background: Cadmium is an inescapable environmental pollutant that permeates the food chain and has been debatably associated with diabetes in humans.

Purpose And Procedures: To probe the specific impact of low-level cadmium exposure on insulin production, largely sub-cytotoxic (50-500 nM) concentrations of cadmium chloride challenged the INS-1 and MIN6 rodent models of pancreatic β-cells for the longest possible time, up to 4 days, before sub-culturing.

Main Findings: The concentration of detectable oxidants, the pattern of the actin cytoskeleton, the translocation of β-catenin, the activity of protein phosphatases, calcium traffic, and the phosphorylation status of several key signaling nodes, such as AMP kinase and mitogen activated kinases including nuclear translocation of Extracellular signal-Regulated Kinase, were all insensitive to the applied very low cadmium doses.