Biomedical subjects

F Benatti

Publications and source records attributed to F Benatti.

3 recordsLinked to original sources

PubMed1998

Inhibition of proteasome function prevents thymocyte apoptosis: involvement of ornithine decarboxylase.

We have previously shown that polyamine levels rapidly decrease in thymocytes undergoing apoptosis, and that ornithine decarboxylase increases early but too transiently to maintain elevated polyamine levels. These data led us to suppose that a precocious ornithine decarboxylase degradation might be responsible for the imbalance of polyamine metabolism. Ornithine decarboxylase is known to be degraded by the cytosolic 26S proteasome that plays an essential role in thymocyte apoptosis. In this paper we demonstrate that the inhibition of proteasome function preserves ornithine decarboxylase activity and prevents thymocytes from undergoing apoptosis after dexamethasone treatment. Since intracellular polyamine levels are also preserved, ornithine decarboxylase seems to be functionally active in maintaining polyamine homeostasis after proteasome inhibition in thymocytes. Our proposed role for the proteasome in quiescent cells upon an apoptotic stimulus is to degrade proteins like ornithine decarboxylase that are involved in the control of the cell cycle and cell survival.

Animals↗

PubMed1996

Successful immunosenescence and the remodelling of immune responses with ageing.

In recent decades, major theoretical and technological advances have been achieved in the field of immunology. These have allowed the scientific community to analyse the immune system in a much more sophisticated manner than was possible even 20 years ago. Moreover, great theoretical changes have also occurred in gerontology-in particular, the hypothesis has been put forward that ageing and diseases are two different phenomena, and that successful ageing, i.e. ageing in good psychophysical conditions, is really possible for most humans and animals. Immunosenescence was then carefully investigated, either in selected healthy people of advanced age or in the oldest old people, such as healthy centenarians. The main results showed that most immune parameters are indeed well preserved even at this far advanced age. This paper deals with some of the most important theoretical problems of immunosenescence. An immunological tenet was that the most important phenomenon of immunosenescence is the involution of the thymus. In most textbooks and papers it is taken for granted that the thymus starts its involution immediately after puberty. When people aged 60-65 were considered old, it was not difficult to think that they could live for the rest of their life with a fully involuted thymus. The findings on centenarians challenge this tenet, as they have only a small reduction of T lymphocytes, and a relatively normal number of virgin and memory T cells, together with a functional T cell repertoire. Other observations reported here on centenarians, concerning the activity of B lymphocytes and the cytokine network, as well as those on the well-preserved innate immunity and the cells' capability of undergoing proliferation after appropriate stimuli, suggest that complex immune changes occur with age, but also indicate that we have to modify our attitude, to grasp the new scenario which is emerging. Immunosenescence can no longer be considered as a unidirectional deterioration, and this complex phenomenon is much better described by terms such as 'remodelling', 'reshaping' or 'retuning'.

Aging↗

PubMed1995

Is polyamine decrease a common feature of apoptosis? Evidence from gamma rays- and heat shock-induced cell death.

Here we report that in rat thymocytes undergoing apoptosis upon two different stimuli, such as heat shock treatment and gamma irradiation, an early mRNA accumulation of ornithine decarboxylase (ODC)--the rate-limiting enzyme of polyamine biosynthesis--was followed by a very marked increase in ODC activity (28-40 and 6-8-fold, respectively). However, polyamine levels started to decrease before the appearance of DNA laddering, being putrescine and spermidine strongly diminished (8-12 hs), and spermine even depleted (12 hs). Taken together with our previous data on another model of apoptosis, i.e., glucocorticoid-induced cell death (Desiderio et al., Cell Growth Differ. 6: 505-513, 1995), these results suggest that an imbalance of polyamine metabolism, i.e., a strong activation of ODC and a paradoxical decrease of the intracellular polyamine content, might be a general feature of the apoptotic process.

Analysis of Variance↗