Alpha-tocopherol but not 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (trolox or CTMC) and 2,2,5,7,8 pentamethyl-6-hydroxy chromane (PMC), derivatives of αtocopherol, inhibited the superoxide (O2-) generation of rat peritoneal neutrophils (RPMN) induced by phorbol 12-myristate 13-acetate (PMA). ID50 for neutrophils obtained from the peritoneal cavity of rat and guinea pig was about 1μM. This concentration, however, was much lower than that for the inhibition of PMA-activated phospholipid-dependent protein kinase (PKC) (ID50 = 30 μM). The αtocopherol sensitive O2- generation was also observed in neutrophils induced by dioctanoylglycerol (diC8) and calcium ionophore A23187 but not by formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan (OZ) and sodium dodecyl sulfate (SDS). The pattern of inhibition by αtocopherol was quite similar to that of staurosporine, a specific inhibitor of PKC. The αtocopherol content of RPMN was 12 ng/106 cells and a linear increase to 200 ng/106 cells by addition of αtocopherol to the cell suspension corresponded with an increased inhibition of O2- generation. These results indicate that both the chemical structure and the content of αtocopherol might be important factors in O2- generation by neutrophils.
- Protein kinase C inhibitor
ASJC Scopus subject areas