Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively

Disruption of Retinoic Acid Receptor Alpha Reveals the Growth Promoter Face of Retinoic Acid

Retinoic acid (RA), the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs), exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591). The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER), the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P), the sphingolipid with prosurvival activity.We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase)-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling.In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct, yet integrated processes apparently concur to the growth-promoter effects of RA

Le potenzialità della filiera foresta-legno in Sicilia

Dalla seconda metà del secolo scorso il patrimonio forestale della Sicilia è aumentato in termini di superficie. L’aumento recente è stato favorito dai processi di rinaturalizzazione degli ex coltivi e dei pascoli e dalla disponibilità di fondi europei per i rimboschimenti e l’arboricoltura da legno, insieme all’adozione di nuove politiche rivolte alla sostenibilità ambientale. Tuttavia, tale incremento della risorsa nella maggior parte dei casi non è stato un affiancato da uno sviluppo delle politiche e delle azioni mirate a promuovere la gestione forestale, tantomeno la valorizzazione dei prodotti legnosi e non. Tale carenza di politiche efficaci nel contesto italiano, in particolare l’applicazione nel territorio siciliano, dove il tasso di produzione interna di legno è tra i più bassi in Europa, si è verificata non solo riguardo la produzione ma anche la tutela dell’assetto idrogeologico e la difesa del territorio. L’anello più debole della filiera legno in Sicilia è quello che riguarda le prime fasi della catena produttiva, dalla gestione della risorsa forestale stessa ai settori delle utilizzazioni e della prima trasformazione. Ciò è dovuto principalmente alla carenza di infrastrutture e in particolare di un’adeguata viabilità forestale, ma anche al limitato valore qualitativo degli attuali prodotti e alla domanda di materia prima legnosa nettamente superiore rispetto all’offerta interna, oltre alla presenza di una elevata e stabile offerta estera di materiale spesso qualitativamente superiore importato a prezzi competitivi. Inoltre la filiera foresta-legno in Sicilia presenta fondamentalmente un grave deficit nell’organizzazione e nel coordinamento fra i diversi segmenti che la compongono, caratterizzati da gradi di sviluppo diversi. Tuttavia, la filiera produttiva legata alla risorsa legno, presenta importanti opportunità di crescita e sviluppo dal punto di vista produttivo e occupazionale, sia a monte che a valle della filiera stessa, motivo per cui si dovrebbe intervenire sulla pianificazione e gestione delle stesse, al fine di incentivare l’utilizzo della materia prima locale ed al contempo informare i protagonisti del settore dei vantaggi economici che possono trarre da tali possibilità. Scopo del presente lavoro è quello di analizzare il consumo e le potenzialità del legno in Sicilia attraverso indagini di settore e territoriali. La raccolta dei dati è stata effettuata tramite la consultazione di dati ISTAT, Camera di Commercio e associazioni di categoria, tra cui FederLegno. Sono state analizzati i dati disponibili sui consumi regionali di legno e l’identificazione e distribuzione sul territorio siciliano di aziende di utilizzazione e trasformazione del legno. Nonostante la scarsa rappresentatività dei dati e la difficoltà nel reperimento degli stessi è stato delineato un quadro generale del settore relativo all’utilizzazione, al commercio e alla trasformazione del legno in Sicilia

Is autophagy the key mechanism by which the sphingolipid rheostat controls the cell fate decision?

Sphingolipids are major constituents of biological membrane and some of them behave as second messengers involved in the cell fate decision. Ceramide and sphingosine 1-phosphate (S1P) constitute a rheostat system in which ceramide promotes cell death and S1P increases cell survival. We have shown that both sphingolipids are able to trigger autophagy with opposing outcomes on cell survival. Here we discuss and speculate on the diverging functions of the autophagic pathways induced by ceramide and S1P, respectively

ANALISI FENOMENOLOGICA GESTALTICA DELL'ESPERIENZA ESSENZIALE DELLA RABBIA

According to an actual epistemology it is possible to do a scientific work starting from a direct perspective so that, even if the objective approach has been considered as synonymous of scientifically correct, the “subjective” approach will be necessarily based on the direct observation of the experience itself. The phenomenological approach considers emotion as a peculiar consciousness phenomenon different from pure thinking: it aims to establish emotion comprehension on objective basis. Emotion is not an idea or a thought, it is the very inception and it has pre-rational nature.The phenomenological approach becomes an essential condition for a scientific method of analysis. One of the main principles of the Gestalt Theory is that the Self “gets to-gether” when it becomes a whole form together with the world thus the phenomenological approach becomes the true and natural technique to get a scientific knowledge of perception, or the way the Self enters in contact with the world. The Gestalt-therapy is based on: consciousness development, experimental approach, to work here and now, the phenomenological practice, to work with incarnation. This methodological approach of the Gestalt-therapy arises from the purpose to integrate all emotional experience perceived by the subject, connecting perception with thinking and therefore with feelings. The objective is to shape the phenomenological research on the gestalt principles and on an integrated methodology. The focus was especially brought on the subjective description of anger as emotional experience, distinguishing five prototypes: Explosive Anger, Underestimating Anger, Manipulative Anger, Daring Anger and Refusal Anger

Regulation of autophagy by sphingosine kinase 1 and its role in cell survival during nutrient starvation.

The sphingolipid ceramide induces macroautophagy (here called autophagy) and cell death with autophagic features in cancer cells. Here we show that overexpression of sphingosine kinase 1 (SK1), an enzyme responsible for the production of sphingosine 1-phosphate (S1P), in MCF-7 cells stimulates autophagy by increasing the formation of LC3-positive autophagosomes and the rate of proteolysis sensitive to the autophagy inhibitor 3-methyladenine. Autophagy was blocked in the presence of dimethylsphingosine, an inhibitor of SK activity, and in cells expressing a catalytically inactive form of SK1. In SK1(wt)-overexpressing cells, however, autophagy was not sensitive to fumonisin B1, an inhibitor of ceramide synthase. In contrast to ceramide-induced autophagy, SK1(S1P)-induced autophagy is characterized by (i) the inhibition of mammalian target of rapamycin signaling independently of the Akt/protein kinase B signaling arm and (ii) the lack of robust accumulation of the autophagy protein Beclin 1. In addition, nutrient starvation induced both the stimulation of autophagy and SK activity. Knocking down the expression of the autophagy protein Atg7 or that of SK1 by siRNA abolished starvation-induced autophagy and increased cell death with apoptotic hallmarks. In conclusion, these results show that SK1(S1P)-induced autophagy protects cells from death with apoptotic features during nutrient starvation