title: Thiol proteinase inhibitors reverse the increased protein kinase C down-regulation and concanavalin A cap formation in polymorphonuclear leukocytes from Chediak-Higashi syndrome (beige) mouse.
abstract: Protein kinase C (PKC) plays an essential role in intracellular signal transduction for various cell functions, including concanavalin A (Con A)-induced cap formation. This enzyme is known to be proteolysed by calpain, which is a Ca2(+)-dependent thiol proteinase. As reported previously, in polymorphonuclear leukocytes (PMNs) from beige mouse, the model of Chediak-Higashi syndrome, Con A-induced cap formation significantly increased compared with that in normal mouse. However, after pretreatment of beige PMNs with the thiol proteinase inhibitors leupeptin or E-64, the capping decreased to normal levels. Meanwhile, Con A-induced the translocation of PKC from the cytosolic to membrane fraction within 5 min in both mice, which is essential to the activation of this enzyme. However, after the translocation, an abnormal rapid decline in membrane-bound PKC activity was noted in beige mouse PMNs. Both leupeptin and E-64 also corrected the rapid decline in PKC activity observed in the beige mouse. These findings suggest that the normalization of Con A cap formation in beige mouse PMNs by the thiol proteinase inhibitors is associated with the correction of abnormality in PKC activity.
authors.affiliation: Department of Bacteriology, Fukushima Medical College, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sato
authors.forename: F
authors.initials: F
authors.lastname: Tanabe
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: E
authors.initials: E
authors.lastname: Ishida
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
mesh_terms: D000818:Animals; D002154:Calpain / Q000032:analysis / Q000037:antagonists & inhibitors*; D002609:Chediak-Higashi Syndrome / Q000097:blood*; D003208:Concanavalin A / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D007152:Immunologic Capping / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D011493:Protein Kinase C / Q000097:blood*
chemical_list: D003208:Concanavalin A; D011493:Protein Kinase C; D002154:Calpain