Vulnerability of mitochondrial complex I in PC12 cells exposed to manganese.

The present findings provide experimental evidence for the hypothesis that an impairment of mitochondrial function may be involved in manganese neurotoxicity. Specifically, the treatment of dopaminergic neuronal-derived cell line (PC12) with MnCl2 produced a significant inhibition of some mitochondrial complexes of the respiratory chain, while in the glial-derived cell line (C6) this effect was not observed. In PC12 the decrease in complex I activity was more pronounce than in other mitochondrial complexes. However treatment of cells with ZnSO4 exerted no significant variations in enzymatic activities. A direct exposure of mitochondrial fraction to MnCl2 reduced enzymatic activities of mitochondria in both cell lines adding further support to the proposed theory that the different sensitivity of the cells to manganese may be explained by a difference in uptake or intracellular storage. These data indicate that manganese neurotoxicity could be the result of a direct effect just on complex I activity or due to a secondary effect of oxidative stress induced by an excess of this transition metal.

Benomyl affects the microtubule cytoskeleton and the glutathione level of mammalian primary cultured hepatocytes.

Rat primary hepatocyte cultures have been used to study the effect of Benomyl alone or in combination with Pirimiphos-methyl. The results presented demonstrate that Benomyl alone is responsible for the microtubular disorganization in both a time- and dose-dependent manner, that the effect is reversible after the agent is removed, and that Benomyl is a potent glutathione-depleting agent. Pirimiphos-methyl, alone or combined with Benomyl had no effect on microtubule organization, but reinforced the decrease in glutathione.

Mitochondrial toxicity of iron and the protective role of ferritin on dopaminergic PC12 cell line.

A specific defect of imtochondrial Complex I activity has recently been identified in the substantia nigra of parkinsonian brain. Using an in vitro dopaminergic PC12 cell line model, a possible pathogenic link has been investigated between this finding and increased levels of iron actually observed in the substantia nigra of parkinsonian patients. Exposure of PC12 cells to FeSO(4) for 168 hr induced a significant inhibition of Complex I, whereas succinate dehydrogenase activity was not reduced by this treatment. Furthermore, the non-dopaminergic cell line (SK-N-BE) was not sensitive to the mitochondria! inhibitory effect of iron. Direct treatment of the mitochondrial fraction with FeSO(4) decreased Complex I activity in both cell lines, suggesting that the difference in sensitivity of cells to iron could be due to the difference in uptake or intracellular storage of this element.

Effects of level of acoustic stimulation on locomotor activity in the gerbil.

Two experiments dealt with the behavioral responsiveness of the Mongolian gerbil to the onset, offset, and intensity of auditory stimulation. In Experiment I, the presence of background noise, relative to a condition of silence, was found to facilitate rate of shuttle activity in the gerbil. Also, both incremental and decremental shifts in noise intensity produced immediate increases and decreases, respectively, in activity level. Experiment II revealed that the relationship between shuttle-activity level and background noise intensity was nonmonotonic over the 60-90 dB range, with optimal facilitation manifested at 80 dB SPL. A similar trend was observed with running-wheel activity. Finally, in both experiments substantial habituation of general activity was obtained. The results were discussed in terms of theoretical conceptions of the energizing properties of environmental stimulation (e.g. , arousal theory, stimulus intensity dynamism) and psycho-physiological reactions of the gerbil to auditory stimulation.

Rearrangements on chromosomes 7 and 14 with breakpoints at 7q35 and 14q11 in angioimmunoblastic lymphadenopathy and IBL-like T-cell lymphoma.

In this report we discuss some cases of AILD and IBL-like T-cell lymphomas and attempt to clarify the cytogenetic relationship between these complex disease states. During the period 1980-1987 we have studied No. 6 patients affected with AILD, three of which showed final evolution into Immunoblastic T-cell lymphoma. Cytogenetic studies, carried out on surgical lymphonodal material with histological diagnosis of AILD and leukemic cells obtained from the peripheral blood at the time of diagnosis, were analysed with IBAS 2000 for a computerized analysis, according to ISCA 1978 criteria. We have found similar translocations in three of our patients with AILD and terminal T-cell immunoblastic lymphoma, occurring between chromosomes 7 and 14 with breakpoints at 7q35 and 14q11. The arising of T-cell lymphoma in patients with AILD seems to be related to the presence of clonal cells with abnormal 7:14 translocation, which represent a very sensible marker of clonality desides of T-cell maturational lineage. In our opinion, the forms of AILD with these cytogenetic aberrations are pre-lymphomatous lesions. On the contrary, the lack of such rearrangements is indicative of non-neoplastic patterns.