Tissue coenzyme Q (ubiquinone) and protein concentrations over the life span of the laboratory rat.

The coenzyme Q (ubiquinone) concentrations of a number of tissues have been determined over the life span of the male laboratory rat. Coenzyme Q increased between 2 and 18 months and decreased significantly at 25 months in the heart and kidney, and the gastrocnemius, oblique and deep aspect (red) vastus lateralis muscles. The coenzyme Q concentration of liver increased over the life span, while it remained relatively constant in brain, lung, and the superficial aspect (white) of the vastus lateralis muscle. Data are also included for organ weights and protein contents of tissues over the life span. The various roles of coenzyme Q in cellular electron transfer and its regulation, energy conservation in oxidative phosphorylation, and its clinical efficacy in diseases of energy metabolism are discussed. It is hypothesized that coenzyme Q serves as a free radical quencher in the mitochondrion, a major site of free radical formation, in addition to its other roles in cellular energy metabolism, and that its cellular diminution may contribute to the loss of cellular function accompanying ageing.

Phorbol myristate acetate inhibits growth in S49 cells: isolation of resistant variants.

We have used S49 mouse lymphoma cells to study phorbol ester effects on growth. Treatment of wild-type (wt) cells with phorbol 12-myristate 13-acetate (PMA) results in growth arrest within 72 hr. We have selected variants that are resistant to PMA-induced growth arrest, based on a selection in the presence of 10 nM PMA. We have characterized one of these variants, termed 21.1, in detail. The 21.1 and wt cells contain similar levels of protein kinase C (PKC) as determined by [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding. Treatment of both wt and 21.1 cells with PMA results in translocation of PKC to the membrane, suggesting that the coupling between PKC and an immediate biological response is intact. PMA treatment leads to the phosphorylation of many similar proteins in wild-type and 21.1 cells. However, in the 21.1 cells there is a prominent substrate of approximately 70 kilodaltons (kD) which is no longer phosphorylated after PMA treatment. In wild-type cells ornithine decarboxylase (ODC) activity and mRNA levels are decreased within 1 hr of PMA treatment. Likewise, ODC levels are decreased in the 21.1 cells after exposure to PMA even though PMA only slightly modulates the growth of these cells. The 21.1 cells represent a unique line with a dominant phenotype in which ODC expression is uncoupled from the growth state of the cell. These cells may represent a good model system in which to examine the steps involved in phorbol ester growth regulation in S49 cells.

Overexpression of the neurotrophic cytokine S100 beta in human temporal lobe epilepsy.

Neuritic sprouting and disturbances of calcium homeostasis are well described in epilepsy. S100 beta is an astrocyte-derived cytokine that promotes neurite growth and induces increases in levels of intracellular calcium in neurons. In sections of neocortex of surgically resected temporal lobe tissue from patients with intractable epilepsy, we found that the number of S100 beta-immunoreactive astrocytes was approximately threefold higher than that found in control patients (p < 0.001). These astrocytes were activated, i.e., enlarged, and had prominent processes. Temporal lobe tissue levels of S100 beta were shown by ELISA to be fivefold higher in 21 epileptics than in 12 controls (p < 0.001). The expression of the astrocyte intermediate filament protein, glial fibrillary acidic protein, was not significantly elevated in epileptics, suggesting a selective up-regulation of S100 beta expression. Our findings, together with established functions of S100 beta, suggest that this neurotrophic cytokine may be involved in the pathophysiology of epilepsy.