Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

Pb(II) Induces Scramblase Activation and Ceramide-Domain Generation in Red Blood Cells

Blog Article

Abstract The mechanisms of Pb(II) toxicity have been studied in human red blood cells using confocal microscopy, immunolabeling, fluorescence-activated cell sorting and atomic force microscopy.The process follows a sequence of events, starting with calcium entry, followed by potassium release, morphological change, generation of ceramide, lipid flip-flop and finally cell lysis.Clotrimazole blocks potassium channels and the whole process Easter Ornament is inhibited.

Immunolabeling reveals the generation of ceramide-enriched domains linked to a cell morphological change, while the use of a neutral sphingomyelinase inhibitor greatly delays the process after the morphological change, and lipid flip-flop is significantly reduced.These facts point to three major checkpoints in the process: first the upstream exchange of calcium and potassium, then ceramide domain formation, and finally the downstream scramblase activation necessary for cell lysis.In addition, partial non-cytotoxic cholesterol depletion of red blood cells accelerates the process as the morphological change occurs faster.

Cholesterol could have a HYALURONIC ACID role in modulating the properties of the ceramide-enriched domains.This work is relevant in the context of cell death, heavy metal toxicity and sphingolipid signaling.