A genetikai diabeteskockázat hatása a csontanyagcsere–energia-háztartás kapcsolatokra

Absztrakt Bevezetés: A 2-es típusú cukorbetegség fokozott csonttörési kockázattal jár, hiányzik a cukoranyagcsere és a csontátépülés közötti kapcsolat. Nem ismert, hogy ez a romló anyagcserehelyzet miatt alakul ki vagy a diabetes genetikai kockázatának része. Célkitűzés: A szerzők 2-es típusú cukorbetegekben e kapcsolat hiányának hátterét kívánták tisztázni. Módszer: A cukorterhelések és hyperinsulinaemiás-normoglykaemiás klemp alapján 18 egészséges, de a 2-es típusú cukorbetegség genetikai kockázatát hordozó nőt (családban elsőfokú 2-es típusú cukorbeteg rokon) hasonlítottak 26 negatív családi anamnézisű egészséges nőhöz. Eredmények: Az egésztest-cukorfelhasználás és a csont metabolikus egységei közötti kapcsolat a diabetes genetikai kockázatát hordozó nőkben hiányzott, amint a manifeszt cukorbetegekben is. A kockázati csoportban csökkent a nagy molekulájú, kis denzitású és nőtt a kis molekulájú, magas denzitású LDL-molekulák mennyisége, ami gyulladásos citokinszaporulattal és a csontbontás túlsúlyával társult. Következtetések: Az eredmények alapján a kapcsolat hiánya nem a romló inzulinérzékenység és romló anyagcserehelyzet következménye, hanem a genetikai kockázat egyik jellegzetessége. A glükózintolerancia és az inzulinrezisztencia kialakulását megelőző lipideltérés oka nem ismert. Orv. Hetil., 2015, 156(25), 1007–1013

The Homolog of the Five SH3-Domain Protein (HOFI/SH3PXD2B) Regulates Lamellipodia Formation and Cell Spreading

Motility of normal and transformed cells within and across tissues requires specialized subcellular structures, e.g. membrane ruffles, lamellipodia and podosomes, which are generated by dynamic rearrangements of the actin cytoskeleton. Because the formation of these sub-cellular structures is complex and relatively poorly understood, we evaluated the role of the adapter protein SH3PXD2B [HOFI, fad49, Tks4], which plays a role in the development of the eye, skeleton and adipose tissue. Surprisingly, we find that SH3PXD2B is requisite for the development of EGF-induced membrane ruffles and lamellipodia, as well as for efficient cellular attachment and spreading of HeLa cells. Furthermore, SH3PXD2B is present in a complex with the non-receptor protein tyrosine kinase Src, phosphorylated by Src, which is consistent with SH3PXD2B accumulating in Src-induced podosomes. Furthermore, SH3PXD2B closely follows the subcellular relocalization of cortactin to Src-induced podosomes, EGF-induced membrane ruffles and lamellipodia. Because SH3PXD2B also forms a complex with the C-terminal region of cortactin, we propose that SH3PXD2B is a scaffold protein that plays a key role in regulating the actin cytoskeleton via Src and cortactin

Environmental factors shaping the distribution of common wintering waterbirds in a lake ecosystem with developed shoreline

In this study, we tested whether the spatial distribution of waterbirds is influenced by shoreline urbanization or other habitat characteristics. We conducted monthly censuses along shoreline sections of a continental lake (Lake Balaton, Hungary) to assess the abundance of 11 common species that use this lake as a feeding and staging area during migration and winter. We estimated the degree of urbanization of the same shoreline sections and also measured other habitat characteristics (water depth, extent of reed cover, biomass of zebra mussels, distances to waste dumps and to other wetlands). We applied linear models and model averaging to identify habitat variables with high relative importance for predicting bird distributions. Bird abundance and urbanization were strongly related only in one species. Other habitat variables exhibited stronger relationships with bird distribution: (1) diving ducks and coots preferred shoreline sections with high zebra mussel biomass, (2) gulls preferred sites close to waste dumps, and (3) the abundances of several species were higher on shoreline sections close to other wetlands. Our findings suggest that the distribution of waterbirds on Lake Balaton is largely independent of shoreline urbanization and influenced by food availability and connectivity between wetlands

FSP1 is a glutathione-independent ferroptosis suppressor

Ferroptosis is an iron-dependent form of necrotic cell death marked by oxidative damage to phospholipids1,2. To date, ferroptosis has been believed to be controlled only by the phospholipid hydroperoxide-reducing enzyme glutathione peroxidase 4 (GPX4)3,4 and radical-trapping antioxidants5,6. However, elucidation of the factors that underlie the sensitivity of a given cell type to ferroptosis7 is critical to understand the pathophysiological role of ferroptosis and how it may be exploited for the treatment of cancer. Although metabolic constraints8 and phospholipid composition9,10 contribute to ferroptosis sensitivity, no cell-autonomous mechanisms have been identified that account for the resistance of cells to ferroptosis. Here we used an expression cloning approach to identify genes in human cancer cells that are able to complement the loss of GPX4. We found that the flavoprotein apoptosis-inducing factor mitochondria-associated 2 (AIFM2) is a previously unrecognized anti-ferroptotic gene. AIFM2, which we renamed ferroptosis suppressor protein 1 (FSP1) and which was initially described as a pro-apoptotic gene11, confers protection against ferroptosis elicited by GPX4 deletion. We further demonstrate that the suppression of ferroptosis by FSP1 is mediated by ubiquinone (also known as coenzyme Q10 (CoQ10)): the reduced form, ubiquinol, traps lipid peroxyl radicals that mediate lipid peroxidation, whereas FSP1 catalyses the regeneration of CoQ10 using NAD(P)H. Pharmacological targeting of FSP1 strongly synergizes with GPX4 inhibitors to trigger ferroptosis in a number of cancer entities. In conclusion, the FSP1–CoQ10–NAD(P)H pathway exists as a stand-alone parallel system, which co-operates with GPX4 and glutathione to suppress phospholipid peroxidation and ferroptosis