| Popis: |
Abstract: Cells maintain an intracellular environment that is reducing in the face of an oxidizing extracellular environment. Regulated alterations in the intracellular redox state (redox signalling) can modulate events such as DNA synthesis, enzyme activation. selective gene expression and regulation of the cell cycle. The primary consequence ol intracellular redox signalling is a change in the oxidation state of cysteine residues ol key proteins. This review will examine a number of the cellular redox systems which are in place It' control the redox state, including such proteins as glutathione and glutathione reductase. thioredoxin and thioredoxin reductase, the highly cysteine rich, metalothioneins and the Ref-I protein which plays a role in the activity of AP-I and NF-KB. Signalling processes will be: iJ.:111ificd which are dependent on the redox state of controlling proteins and are potential targets for drug development and include transcription factors whose activation is a prerequisite for growth factor stimulated growth. The development of drugs which exploit the cellular redox state has grown dramatically over the last few years as the understanding of cellular redox has burgeoned. This review will attempt to present the current state of knowledge of agents in this category including those which exploit the hypoxic cellular environment, those which participate through antioxidant pathways and the evolving area of interest involving agents which alter the signalling process through protein thioalkylation. |
