Internation of zinc ions with DNA-dependent RNA polymerases A, B and C isolated from calf thymus

Abstract

Purified DNA-dependent RNA polymerases A, B and C isolated from calf thymus contain a significant amount of zinc. Atomic absorption spectroscopy revealed the presence of 6.7, 5.35 and 2.6--4.1 g-atoms of zinc per mole of polymerase A, B and C, respectively. These enzymes are inhibited by treatment with 1,10-phenanthroline at concentrations varying from 10(-5) to 10(-4) M. However, the addition of zinc ions does not restore fully the activity of 1,10-phenanthroline treated enzymes. Exogenous zinc ions reduce in vitro an overall RNA synthesis catalysed by RNA polymerases from calf thymus. In addition to the sites which bind zinc in a specific and stoichiometric way these enzymes possess other classes of binding sites with high and low affinity. Occupancy by exogenous zinc of these additional binding sites inhibit polymerase activity.

Roles of Zinc Signaling in the Immune System

“…ZnD induces thymic atrophy and lymphopenia and depresses both innate and adaptive immune responses: it impairs phagocytosis, intracellular killing activity, and cytokine production by macrophages; host defense by neutrophils and natural killer cells; and the proliferation, cytokine production, and antibody secretion of T and B cells [5]. These outcomes, which appear to be mostly rooted in the dysregulation of basic cellular functions such as DNA replication, RNA transcription, and cell activation, proliferation, differentiation, and survival [6–11], result in an increased susceptibility to a wide range of infectious agents and a longer duration of infection [1, 5]. …”