A novel role of protein kinase C-delta in cell signaling triggered by glutathione depletion.
Current evidence demonstrates that protein kinase C (PKC) belongs to a group of cell-signaling molecules that are sensitive targets for redox modifications and functional alterations that mediate oxidant-induced cellular responses. Our studies have demonstrated that diminished intracellular GSH was associated to inactivation of classic isoforms and increased activity of novel PKCs, and triggered molecular signals important for cell survival. Loss of GSH and oxidative damage are probably an early signaling event in apoptotic death, which is characterized by the activation of PKC-delta. Apoptotic process consequent to GSH depletion was inhibited by rottlerin, a PKC-delta-specific inhibitor, which exerted a negative effect on oxyradical production. Therefore, it may be concluded that PKC-delta activity is related to reactive oxygen species production and is involved in the pathway leading to apoptosis and growth arrest.
Domenicotti
Cinzia
C
Section of General Pathology, Department of Experimental Medicine, University of Genova, via L.B. Alberti, 2, 16132 Genoa, Italy. cdomeni@medicina.unige.it
Marengo
Barbara
B
Nitti
Mariapaola
M
Verzola
Daniela
D
Garibotto
Giacomo
G
Cottalasso
Damiano
D
Poli
Giuseppe
G
Melloni
Edon
E
Pronzato
Maria A
MA
Marinari
Umberto M
UM
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001578:Benzopyrans / Q000494:pharmacology; D002478:Cells, Cultured; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D051745:Protein Kinase C-delta; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D000098:Acetophenones; D001578:Benzopyrans; D017382:Reactive Oxygen Species; C085746:rottlerin; C497260:Prkcd protein, rat; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D005978:Glutathione