Oxidative stress may induce reduction of brain transmitter content in pacific salmon

Abstract

Insulin-dependent diabetes mellitus (IDDM) is caused by macrophage, T-cell, B e l l and humoral factor mediated damage of the insulin-producing &cells of the islets of Langerhans. Okamoto (1981. Mol Cell Bwchem 37 43-61)proposed a unifying model for the mechanism of b l l destruction. Central to this model are breaks in nuclear DNA of pcells, inducing activation of the enzyme poly (ADP-ribose) synthetase (PARS), which poly ADP-rib0sylate.s nuclear proteins using NAD+ as a substrate. As a result inhacellular NAD+ & ATP levels fall dramatically, initially inhibiting insulin secretion and eventually resulting in p-cell death. We have evidence from studies w i t h both primary islet cells (isolated from male Wistar rats) and the insulin sccfeting gcell lines, BRIN BD11 and CRI-G1.that there is an increase in DNA fragmentation followed by an increase in cell death when p-cells are incubated in the presence of newly diagnosed diabetic serum. These results support the findings of Bcrggren et OL (1993, Science 261 86-90). We propose that kcell death can result fmm complement activation in diabetic serum due to the pnsence of complement binding auto antibodies. We report that protection of the b e l l s from D D M serum induced cell death can be achieved by provision of the metabolic fuel glutamine, which may boost intracellular ATP. and Philip Newsholme c58 Oxidative stress may induce reduction of brain transmitter content in pacific salmon Pacific salmon (Oncorhynchus) die after oceanic migration and spawning in their natal stream. Their body tissues feed the local microfauna which, in turn, is the food source of their offspring. The molecular background of this pre-programmed death is undetermined and it has been speculated that salmon can serve as a unique model for studies into vertebrate aging. The trigger mechanisms of salmon aging could be based on changes in brain functions. Thus, we investigated concentrations of protein, biogenic amines, and indices of oxidative stress (glutathione, GSH; glutathione disulfide, GSSG) in the brain of the .Red" salmon at 4 stages in its life. All neurotransmitters declined with age. Particularly low levels of GSH and high levels of GSSG preceded the decline of brain protein. This could be indicative of oxidative stress operative early in adult pacific salmon life, at a time when it is still in the ocean, setting the scene for a drastic loss of biogenic amines and, ultimately, for metamorphosis and a rapid deterioration of the entire body. Thus, we think that oxidative stress is an early event in a programmed decline of brain function, which we are now investigating on a histochemical basis. CS9 FUNCTIONAL During the host response to innammation or tissue injury, there are many changes in intermediary metabolism including a dramatic increase in the concentration of the acute phase proteins. We previously reported that acute phase proteins(fibrin0gen; C-reactive protein, CRP; al-acid glycoprotein, AGP) known to be synthesized only in hepatocytes and hepatoma cells, were expressed in...