Redox regulation of cardiac protein kinase C

The two extremes of redox stress imposed on cardiac tissue under ischemia and reperfusion change the redox potential of the cells and affect numerous redox-sensitive molecules, including the ones involved in intracellular communication. Protein kinase C (PKC), a key signalling kinase, is one of those subject to redox control. Activation of PKC by oxidation represents a new paradigm of the alternate signalling principle. Reactive oxygen species act directly on PKC, releasing chelated Zn(2+) ions from the zinc finger of the regulatory domain. Zn(2+) release from PKC by oxidative stress has been shown at the level of isolated protein fragments, PKC immune complexes and single cells. Zn(2+) movements have been further characterized in cryosections prepared from adult rat hearts subjected to in vivo stress by global ischemia followed by reperfusion. The morphology of labile zinc in cardiac tissue and zinc release following PKC stimulation with lipid activator are described. The studies lead to an unexpected and intriguing result, suggesting that in addition to serving a structural function, Zn(2+) ions are likely to play a dynamic regulatory role in PKC. The cysteine-rich domains of the serine/threonine kinases are identified as redox sensors. Thus, being an integrated composite of redox signalling systems, free Zn(2+) reflects the protein redox status and serves as a valid biomarker of stressed tissue and its capacity to respond to stimuli.