Glutathione in Cerebral Microvascular Endothelial Biology and Pathobiology: Implications for Brain Homeostasis
Figure 1
Mechanisms of MG-mediated endothelial barrier dysfunction and its protection by GSH. MG-induced endothelial barrier dysfunction can be caused by MG-protein crosslinking (glycation) resulting in the formation of MG-protein adducts, such as tight junction occludin and basement membrane type IV collagen. MG-protein glycation can also modify the proteasomal and chaperone functions. ROS generated during protein glycation can further mediate barrier dysfunction through various pathways: (a) increased intracellular [Ca2+], (b) direct disruption of adherens junction and tight junction, or (c) phosphorylation of myosin light chain kinase and altered endothelial cell contraction. Protection of barrier integrity is mediated by GSH, which functions as a cofactor in glyoxalase I-catalyzed metabolism of MG. MG: methylglyoxal, GSH: reduced glutathione, : superoxide anion, H2O2: hydrogen peroxide, ROS: reactive oxygen species, AJ: adherens junction, TJ: tight junction, MLCK: myosin light chain kinase.
