Catestatin Improves Post-Ischemic Left Ventricular Function and Decreases Ischemia/Reperfusion Injury in Heart

The Chromogranin A (CgA)-derived anti-hypertensive peptide catestatin (CST) antagonizes catecholamine secretion, and is a negative myocardial inotrope acting via a nitric oxide-dependent mechanism. It is not known whether CST contributes to ischemia/reperfusion injury or is a component of a cardioprotective response to limit injury. Here, we tested whether CST by virtue of its negative inotropic activity improves post-ischemic cardiac function and cardiomyocyte survival. Three groups of isolated perfused hearts from adult Wistar rats underwent 30-min ischemia and 120-min reperfusion (I/R, Group 1), or were post-conditioned by brief ischemic episodes (PostC, 5-cycles of 10-s I/R at the beginning of 120-min reperfusion, Group 2), or with exogenous CST (75 nM for 20 min, CST-Post, Group-3) at the onset of reperfusion. Perfusion pressure and left ventricular pressure (LVP) were monitored. Infarct size was evaluated with nitroblue-tetrazolium staining. The CST (5 nM) effects were also tested in simulated ischemia/reperfusion experiments on cardiomyocytes isolated from young-adult rats, evaluating cell survival with propidium iodide labeling. Infarct size was 61 ± 6% of risk area in hearts subjected to I/R only. PostC reduced infarct size to 34 ± 5%. Infarct size in CST-Post was 36 ± 3% of risk area (P < 0.05 respect to I/R). CST-Post reduced post-ischemic rise of diastolic LVP, an index of contracture, and significantly improved post-ischemic recovery of developed LVP. In isolated cardiomyocytes, CST increased the cell viability rate by about 65% after simulated ischemia/reperfusion. These results suggest a novel cardioprotective role for CST, which appears mainly due to a direct reduction of post-ischemic myocardial damages and dysfunction, rather than to an involvement of adrenergic terminals and/or endothelium

Regolazione dell'orologio circadiano nei mammiferi mediante sumoylazione dell'attivatore trascrizionale BMAL1

4 Abstract The molecular machinery that governs circadian rhythmicity is based on clock proteins organized in regulatory feedback loops. Although posttranslational modification of clock proteins is likely to finely control their circadian functions, only limited information is available to date. Here, we show that BMAL1, an essential transcription factor component of the clock mechanism, is SUMOylated on a highly conserved lysine residue (Lys259) in vivo. BMAL1 shows a circadian pattern of SUMOylation that parallels its activation in the mouse liver. SUMOylation of BMAL1 requires and is induced by CLOCK, the heterodimerization partner of BMAL1. Ectopic expression of a SUMOdeficient BMAL1 demonstrates that SUMOylation plays an important role in BMAL1 circadian expression and clock rhythmicity. This reveals an additional level of regulation within the core mechanism of the circadian clock.Università della Calabria, Dottorato di Ricerca in Biologia animale, Ciclo XIX, a.a.2005-200

Ruolo del citoscheletro actinico nell’ effetto inotropo negativo indotto dai peptidi CgA-derivati nel cuore di Anguilla anguilla e Rana Esculenta

Dottorato di ricerca in Biologia animale, Ciclo XIX, a.a. 2005-2006Università della Calabri

Il cuore e il rene di "Protopterus dolloi" come modello del riarrangiamento strutturale e molecolare in risposta all'estivazione

Dottorato di ricerca in Bilogia Animale, XX Ciclo,a.a. 2006-2007Università della Calabri

I siagonini del Mediterraneo: indagini eco- e morfo-fisiologiche

Dottorato di Ricerca in Biologia Animale, XVIII Ciclo,a.a.2005-2006Università della Calabri

Sviluppo larvale e prime fasi di metamorfosi dell'ascidia Ciona intestinalis: espressione spaziale e temporale dell'ossido nitrico sintasi, localizzazione e ruolo dell'ossido nitrico

Tesi Dottorato di Ricerca in Biologia animale, Ciclo XIX, a.a.2005 – 2006Università della Calabri