MANGANESE-SUPEROXIDE DISMUTASE IN ENDOTHELIAL-CELLS - LOCALIZATION AND MECHANISM OF INDUCTION

Mechanisms of Mn-superoxide dismutase (Mn-SOD) expression in human umb ilical endothelial cells were investigated by Northern blot analysis, enzyme-linked immunosorbent assay, and immunoelectron microscopy. The Mn-SOD in human endothelial cells was markedly induced by the cytokine s tumor necrosis factor (TNF), interleukin-1, and lipopolysaccharide a s well as by phorbol esters [12-O-tetradecanoylphorbol 13-acetate (TPA )]. The induction was partially blocked by dexamethasone and 1-(5-isoq uinolinylsulfonyl)-2-methylpiperazine, a potent inhibitor of protein k inase C (PKC). In endothelial cells in which PKC had been desensitized to TPA by pretreatment for 24 h, addition of TNF caused overexpressio n of Mn-SOD. These facts suggested that at least two separate signal-t ransducing pathways are involved in expression of the Mn-SOD gene. Imm unoelectron-microscopic studies showed that Mn-SOD was localized to th e mitochondrial matrix of the capillary vascular endothelial cells of cardiac tissues and cultured endothelial cells. Mn-SOD, which is norma lly abundant in endothelial cells relative to other cell types, may pl ay an important protective role against stresses such as ischemia and inflammation.