[Pharmacological modulation of alterations of endothelial cytoskeleton induced by hydrogen peroxyde and by TNF-alpha].
New selenium containing compounds which act as mimics of glutathione peroxidase (GPx) protect vascular endothelial cells (HUVEC) from the toxicity of 140 microM hydrogen peroxide. In the absence of GPx mimic, hydrogen peroxide destroys the tightness of the cellular monolayer and transforms the actin network into compact stress fibers. The pre-treatment of the cells by 4 microM of the lead-compound BXT-51072 for 1 hours inhibits the morphological modifications induced by hydrogen peroxide. This GPx mimic can also prevent the alterations of the endothelial cytoskeleton which are induced by Tumor Necrosis Factor-alpha (TNF-alpha) and which consist in a reorganization of actin filaments with the formation of stress fibers. Fluorescent labeling of polymerized actin has been performed by means of phalloidine coupled with rhodamine. The protective effect of this antioxidant catalyst against the toxicity of hydrogen peroxide and TNF-alpha includes the maintenance of a structural configuration of the cytoskeleton which is required for the function of endothelial barrier.
d'Alessio
P
P
Laboratoire de Biochimie Pharmacologique et Métabolique, INSERM U75, CHU Necker, Paris, France.
Moutet
M
M
Marsac
C
C
Chaudière
J
J
D000975:Antioxidants / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects* / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005979:Glutathione Peroxidase / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D018716:Molecular Mimicry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000975:Antioxidants; D014409:Tumor Necrosis Factor-alpha; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase