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The transcription factor NF-κB was first identified as a regulator of the expression of the kappa light-chain gene in murine B lymphocytes (1). It has a central role in the immunological processes and regulates a wide range of genes in a rapid fashion (2). NF-κB interacts with its inhibitor protein IκB and activation of NF-κB causes it to move into the nucleus and this is controlled by the phosphorylation and subsequent degredation of IκB (3,4). The activated form of NF-κB is a heterodimer, which usually consists of two proteins, a p65 (relA) subunit and a p50 subunit. Other subunits (rel, relB, v-rel, and p52) can also bind to the activated NF-κB and thus can activate different sets of genes. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is associated with increased reactive oxygen species (ROS) generation by mononuclear cells (MNC) and an increased oxidative load, which causes oxidative damage to proteins, lipids and DNA (1-3). Recently, we have demonstrated that glucose challenge causes an increase in ROS generation by MNC and polymorphonuclear cells (PMNL). We have also demonstrated that the suppression of ROS generation by MNC by diphenylene iodonium (DPI), a specific inhibitor of NADPH oxidase and the membrane enzyme that generates the superoxide (O*2-) radical, is significantly diminished in the obese and diabetics when compared with normal subjects (4). The assay system used in our ROS generation studies largely detects the superoxide radical, which is produced by the conversion of molecular O2 by NADPH oxidase (5-6). Thus, it would appear that NADPH oxidase activity increases following glucose challenge and that it is relatively non-suppresible in the obese. NADPH oxidase consists of multiple subunits. Equimolar amounts of p47phox and p67phox in the cytosol combine to a form a highly basic 250 kDa protein. During activation, this complex migrates from the cytosol to the membrane where this complex combines with cytochrome b558, which in turn, consists of gp91phox and p22phox .Rac 2, the fifth component of the enzyme migrates to the membrane in association with p47phox, which without it, is unable to reach the membrane (7-10). [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is an important bio-regulatory molecule in the nervous, immune and cardiovascular systems. The physiological involvement of NO in neuronal transmission, control of vascular tone, and immune response-induced cytostasis as well as the deleterious effects associated with altered levels of NO synthesis (1,2) culminated in the selection of the free-radical gas as "1992 Molecule of the Year" (3). [ABSTRACT FROM AUTHOR]