Heme Oxygenase-1 May Affect Cell Signalling via Modulation of Ganglioside Composition

摘要: Heme oxygenase 1 (Hmox1), a ubiquitous enzyme degrading heme to carbon monoxide, iron, and biliverdin, is one of the cytoprotective enzymes induced in response variety stimuli, including cellular oxidative stress. Gangliosides, sialic acid-containing glycosphingolipids expressed all cells, are involved cell recognition, signalling, membrane stabilization. Their expression often altered under many pathological physiological conditions death, proliferation, differentiation. The aim this study was assess possible role Hmox1 ganglioside metabolism relation content liver brain gangliosides, their distribution, mRNA as well protein key glycosyltransferases were determined knockout mice wild-type littermates. To elucidate underlying mechanisms between metabolism, hepatoblastoma HepG2 neuroblastoma SH-SY5Y lines used for vitro experiments. Mice lacking exhibited significant increase concentrations gangliosides metabolism. A marked shift GM1 from subsinusoidal part intracellular compartment into sinusoidal membranes hepatocytes shown mice. Induction stress by chenodeoxycholic acid resulted GM3, GM2, GD1a cells GM3 GM2 line. These changes abolished with administration bilirubin, potent antioxidant agent. observations closely related stress-mediated sialyltransferase regulated at least partially through kinase C pathway. We conclude that an important factor modulating synthesis distribution vivo which might affect signalling higher organisms.