metallothionein and Shock

Evidence concerning a role for metallothionein (MT) in human disease is reviewed. Current knowledge of MT is juxtaposed with our understanding of the pathogenesis of disease. MT is known to modulate three fundamental processes: 1) the release of gaseous mediators such as hydroxyl radical or nitric oxide; 2) apoptosis, and 3) the binding and exchange of heavy metals such as zinc, cadmium or copper. The capability to specifically manipulate MT levels in cells and in mice is beginning to provide answers regarding how MT could impact complex disease scenarios. Associations among MT and several diseases, including cancer, circulatory and septic shock, coronary artery disease, and Alzheimer's disease have been made. Strong evidence exists that MT modulates the immune system. The primary function of MT remains unknown.

Topics: Animals; Apoptosis; Arthritis, Rheumatoid; Cadmium; Copper; Diabetes Mellitus; Free Radicals; HeLa Cells; Humans; Immune System; Metallothionein; Mice; Models, Biological; Neoplasms; Nervous System Diseases; Nitric Oxide; Protein Binding; Shock; Zinc

In response to specific stresses, such as a heat pulse or the sequence of hypoxia-reoxygenation, each isolated cell (prokaryotic and eukaryotic) that has been studied characteristically alters gene expression to synthesize a set of proteins (heat-shock proteins) that are important for intracellular homeostasis. To determine whether a corresponding response occurs within parenchymal cells in vivo when subjected to the complex stress of circulatory shock, liver biopsy specimens were obtained from a swine model of cardiogenic shock before and after shock/resuscitation. With use of complementary DNA prepared from post-shock/resuscitation messenger RNA, a library was constructed and screened for differential gene expression. Of 32/4000 clones initially screened as positive for induction after shock/resuscitation, six were confirmed positive by Northern blot analysis. The nucleotide sequences of two of these six have been determined, and one has been unambiguously identified as metallothionein.

Topics: Animals; Base Sequence; Blotting, Northern; DNA; Electrophoresis, Agar Gel; Female; Gene Expression Regulation; Liver; Metallothionein; Molecular Sequence Data; Resuscitation; RNA; RNA, Messenger; Shock; Swine