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Full-Text Articles in Medicine and Health Sciences
Arachidonyl Trifluoromethyl Ketone Ameliorates Experimental Autoimmune Encephalomyelitis Via Blocking Peroxynitrite Formation In Mouse Spinal Cord White Matter, Adam C. Vana, Shihe Li, Rachel Ribeiro, Flaubert Tchantchou, Yumin Zhang
Arachidonyl Trifluoromethyl Ketone Ameliorates Experimental Autoimmune Encephalomyelitis Via Blocking Peroxynitrite Formation In Mouse Spinal Cord White Matter, Adam C. Vana, Shihe Li, Rachel Ribeiro, Flaubert Tchantchou, Yumin Zhang
Uniformed Services University of the Health Sciences
Inhibition of phospholipase A2 (PLA2) has recently been found to attenuate the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis (MS). However, the protective mechanisms that underlie PLA2 inhibition are still not well understood. In this study, we found that cytosolic PLA2 (cPLA2) was highly expressed in infiltrating lymphocytes and macrophages/microglia in mouse spinal cord white matter. Although cPLA2 is also expressed in spinal cord neurons and oligodendrocytes, there were no differences observed in these cell types between EAE and control animals. Arachidonyl trifluoromethyl ketone (AACOCF3), …
Distinct Role Of Nitric Oxide And Peroxynitrite In Mediating Oligodendrocyte Toxicity In Culture And In Experimental Autoimmune Encephalomyelitis, S. Li, A. C. Vana, R. Ribeiro, Y. Zhang
Distinct Role Of Nitric Oxide And Peroxynitrite In Mediating Oligodendrocyte Toxicity In Culture And In Experimental Autoimmune Encephalomyelitis, S. Li, A. C. Vana, R. Ribeiro, Y. Zhang
Uniformed Services University of the Health Sciences
Nitric oxide has been implicated in the pathogenesis of multiple sclerosis. However, it is still unclear whether nitric oxide plays a protective role or is deleterious. We have previously shown that peroxynitrite, a reaction product of nitric oxide and superoxide, is toxic to mature oligodendrocytes (OLs). The toxicity is mediated by intracellular zinc release, phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), activation of 12-lipoxygenase (12-LOX) and the formation of reactive oxygen species (ROS). In this study, we found that the donors of nitric oxide, dipropylenetriamine NONOate (DPT NONOate) and diethylenetriamine NONOate (DETA NONOate), protected OLs from peroxynitrite or zinc-induced toxicity. …
Protein Kinase C Mediates Peroxynitrite Toxicity To Oligodendrocytes, Shihe Li, Wen Lin, Flaubert Tchantchou, Ruby Lai, Jie Wen, Yumin Zhang
Protein Kinase C Mediates Peroxynitrite Toxicity To Oligodendrocytes, Shihe Li, Wen Lin, Flaubert Tchantchou, Ruby Lai, Jie Wen, Yumin Zhang
Uniformed Services University of the Health Sciences
Peroxynitrite has been suggested to be the potent oxidant causing toxicity to neurons and oligodendrocytes (OLs). Our previous studies have illustrated that intracellular zinc liberation contributes to peroxynitrite toxicity to mature OLs. In this study, we further investigated the signaling pathways involved in this event and identified protein kinase C (PKC) as an important early signaling molecule. We found that a non-selective PKC inhibitor bisindolylmaleimide-1 blocked OL toxicity induced by a peroxynitrite generator SIN-1 and exogenous zinc. The protective effects were due to its inhibition on ERK1/2 phosphorylation and ROS generation. The same phenomenon was also observed in OLs following …