TNF-alpha induced altered signaling mechanism in human neutrophil.
In the present study we investigated the TNF-alpha induced signal transduction mechanism in human neutrophil. Exogenously added TNF-alpha affects both PKC activity and its translocation from cytosol to the membrane. Endogenous protein phosphorylation pattern is inhibited in TNF-alpha induced neutrophil in Ca-dependent and Ca-independent manner, including a major 47 and 66 kDa cytosolic proteins, which may be implicated in superoxide anion generation. However TNF-alpha dose dependently enhances the expression of zeta-PKC isotype but not the beta-PKC. Morphology and cell cytotoxicity are studied in TNF-alpha treated neutrophil to understand the TNF-alpha induced cell death or apoptosis and these experiment is further confirmed by DNA fragmentation analysis. These results clearly demonstrate that TNF-alpha induces cellular death of human neutrophil at least in part by enhanced expression of Ca-independent zeta-PKC. These observations provide an insight towards understanding the function of zeta-PKC in apoptotic pathway.
Das
S
S
Department of Microbiology, Bose Institute, Calcutta, India.
Bhattacharyya
S
S
Ghosh
S
S
Majumdar
S
S
D017209:Apoptosis / Q000187:drug effects; D001692:Biological Transport; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C