The later activation but not the expression of inducible NOS (nitric oxide synthase)-2 in cytokine-stimulated normal human astrocytes can be inhibited by U0126, a specific inhibitor of MEK-ERK kinases

The later activation but not the expression of inducible NOS (nitric oxide synthase)-2 in cytokine-stimulated normal human astrocytes can be inhibited by U0126, a specific inhibitor of MEK-ERK kinase

Comano\u2019s (Trentino) thermal water interferes with the expression and secretion of vascular endothelial growth factor-A protein isoforms by cultured human psoriatic keratinocytes: A potential mechanism of its anti-psoriatic action.

Thermal balneotherapy with Comano spa's water (CW; Trentino, Italy) is used for psoriasis and other skin disorders but the mechanism(s) of action of this hypotonic water are unknown. Since skin psoriatic manifestations are thought to be angiogenesis-dependent, we assessed CW's effects on the expression and release of VEGF-A protein isoforms by cultured human lesional keratinocytes isolated from skin biopsies performed in 9 patients. Confluent, psoriatic keratinocytes were exposed for 11 days to DMEM, whose chemicals had been dissolved in either deionised water (DW-DMEM, controls) or CW (CW-DMEM, treated cells). As detected by Western immunoblotting (WB), incubation in CW-DMEM elicited, with respect to DW-DMEM, an increase in intracellular and/or cell-bound L-VEGF-A189 and L-VEGF-A165 48 kDa protein isoforms with no concurrent change in L-VEGF-A121 and L-VEGF-A165 45 kDa proteins. Moreover, WB analysis of the secreted VEGF-A (sVEGF-A) proteins showed that the 20 and 15 kDa bands corresponding to different VEGF-A isoforms were directly and remarkably reduced in keratinocyte-conditioned CW-DMEM vs. DW-DMEM. Thus, CW interferes with VEGF-A isoform expression and secretion by the psoriatic keratinocytes. These effects would reduce all VEGF-A-mediated angiogenic, vessel permeabilising, and chemotactic effects, thereby at least in part explaining the beneficial actions of CW balneotherapy on the clinical manifestations of psoriasis

Role-Shifting PKC\u3b6 Fosters Its Own Proapoptotic Destruction by Complexing with Bcl10 at the Nuclear Envelope of Human Cervical Carcinoma Cells: A Proteomic and Biochemical Study

Many features of deadly human cervical cancers (HCCs) still require elucidation. Among HCC-derived cell lines, here we used the C4-I one since its quantitative gene expression pattern most closely mimics invasive HCCs, including protein kinase-Czeta (PKCzeta) overexpression. Via proteomic, bioinformatic, and biochemical approaches we identified 31 and 33 proteins co-immunoprecipitating with PKCzeta from nuclear membranes (NMs) of, respectively, untreated or VP-16-exposed C4-I cells. Such proteins belonged to eight functional groups, whose compositions and relative sizes changed with either context.Of the 56 proteins identified, only eight were shared between the two subproteomes, including Bcl10. Surprisingly, proteins known to associate with Bcl10, like Carma1/3 and Malt1,in so-called CBM signalosomes were absent. Notably, in VP-16-treated C4-I cells,PKCzeta\ub7Bcl10 complexes increasingly accrued at NMs, where PKCzeta phosphorylated Bcl10, as PKCzeta also did in vitro and in cell-free systems, both processes being thwarted by interfering RNA (iRNA) PKCz depletion. Caspase-3 wasassociated with PKCzeta\ub7Bcl10 complexes and proteolyzed PKCzeta leading to its inactivation/destruction; both events were prevented by Bcl10 iRNA suppression. Thus,PKCzeta\u2019s molecular interactions and functional roles changed strikingly according to the untreated or apoptogen-treated cells context, and by complexing with Bcl10, PKCzeta surprisingly favored its own demise, which suggests both proteins as HCCs therapeutic targets

Proteomic investigations into non-syndromic aneurysms of the ascending aorta.

The results of proteomic investigations into non-syndromic aneurysms of the ascending aorta are preliminarily reporte

Effetti dell\u2019acqua termale di Comano sulla sintesi e secrezione di citochine e chemochine in cheratinociti psoriasici in vitro.

Effetti dell\u2019acqua termale di Comano sulla sintesi e secrezione di citochine e chemochine in cheratinociti psoriasici in vitr

Programmed cell death occurs in muscle fibers with mitochondrial dysfunction

Programmed cell death occurs in muscle fibers with mitochondrial dysfunctio