Selective activation of protein kinase C delta in human neutrophils following ischemia reperfusion of skeletal muscle.
Circulatory neutrophils are known to be critical mediators of inflammation and oxidative stress during ischemia reperfusion (I/R) injury. Recent studies have shown an important role for protein kinase C (PKC) in neutrophil survival and function. Activation of specific isotypes of PKC are known to be involved in membrane alteration and motility, oxidative phosphorylation, and apoptosis modulation of neutrophils. However, the role of PKC in neutrophil responses to I/R in the clinical setting has not been studied. In this study, we examined the neutrophil activation of PKC induced by tourniquet-controlled I/R of skeletal muscle in humans. We found that I/R rapidly activates and translocates PKC delta, but not any of the classical forms of PKC (alpha or beta) from cytosol to the particulate fraction of neutrophils. Particulate translocation of PKC delta is sustained up to 4 h after reperfusion and is associated with kinase activity. Postreperfusion activation of PKC delta in neutrophils signals proapoptosis, but does not cause immediate cell death (as revealed by neutrophil morphology study and DNA-laddering assay). This study indicates that calcium-independent novel PKC delta (nPKC delta) might be predominantly involved in regulating membrane functions and survival of neutrophils associated with post-I/R-induced inflammatory oxidative stress.
Huda
Ruksana
R
Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas 77555, USA. rhuda@utmb.edu
Vergara
Leoncio A
LA
Solanki
Daneshvari R
DR
Sherwood
Edward R
ER
Mathru
Mali
M
D000098:Acetophenones / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D018482:Muscle, Skeletal / Q000098:blood supply*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051745:Protein Kinase C-delta; D021381:Protein Transport; D015424:Reperfusion; D015427:Reperfusion Injury / Q000201:enzymology*
D000098:Acetophenones; D001578:Benzopyrans; D004791:Enzyme Inhibitors; C085746:rottlerin; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta