1,721,144 research outputs found
Inositol 1,4,5-trisphosphate and ryanodine receptors mobilize calcium from a common functional pool in human U373 MG cells
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Accumulo di mercurio e metilmercurio in alcuni tessuti di delfini Stenella coeruleoalba spiaggiati lungo le coste della Puglia (1992)
No full textThe sigma-1 receptor antagonist PB212 reduces the Ca2+-release through the inositol (1, 4, 5)-triphosphate receptor in SK-N-SH cells
No full textSigma-1 receptors are specifically located at the endoplasmic reticulum–mitochondrion interface, but upon stimulation by ligands or under prolonged cellular stress, they translocate to other areas of the cell. Sigma-1 receptors are involved in the regulation of intracellular [Ca2+] by affecting the Ca2+-influx or the release from intracellular stores. In SK-N-SH cells, we measured the affinity of 4-methyl-1-[4-(6-methoxynaphthalen-1-yl)butyl]piperidine (PB212) at sigma-1 receptor by using a competition binding assay with specific radioligand; we obtained a Ki value = 316 ± 19 nM. PB212 also showed an antiproliferative effect in SK-N-SH cells (EC50 = 32 ± 4 μM) but had no effect in MCF7 cells, which only express sigma-2 receptor; these findings suggest that PB212 behaves as a sigma-1 receptor antagonist. We have studied the effect of PB212 on Ca2+ homeostasis of the SK-N-SH cell line with the fluorescent probe Fura-2. 100 μM PB212 induced a Ca2+-efflux from the endoplasmic reticulum through the inositol (1, 4, 5)-trisphosphate (IP3) receptor. Moreover, [PB212] ranging from 1 to 100 μM reduced the Ca2+-response, triggered by carbachol or bradykinin that engage the phospholipase C/IP3 pathway; such a response is generally increased by sigma-1 receptor agonists. On the other hand, PB212 did not reduce the Ca2+-response mediated by IP3 in LoVo cells, which do not express neither sigma-1 nor sigma-2 receptors, and in MCF7 cells. The fact that the activity of the sigma-1 receptor can be experimentally modulated by agonists and antagonists supports the intriguing hypothesis that some endogenous molecules, unknown at the moment, modulate the sigma-1 receptor and its cellular targets
Residui di metalli (Hg, Pb, Cd, Cr, Se) in organi e tessuti di alcune specie di delfini (Stenella coeruleoalba, Grampus griseus e Ziphius cavirostris)
No full textCalcium response after stimulation by Substance P of U373 MG cells: inhibition of store-operated calcium entry by protein kinase C
No full textHmtVar: a new resource for human mitochondrial variations and pathogenicity data
Full text linkInterest in human mitochondrial genetic data is constantly increasing among both clinicians and researchers, due to the involvement of mitochondrial DNA (mtDNA) in a number of physiological and pathological processes. Thanks to new sequencing technologies and modern databases, the large amount of information on mtDNA variability may be exploited to gain insights into the relationship between mtDNA variants, phenotypes and diseases. To facilitate this process, we have developed the HmtVar resource, a variant-focused database that allows the exploration of a dataset of over 40 000 human mitochondrial variants. Mitochondrial variation data, initially gathered from the HmtDB platform, are integrated with in-house pathogenicity assessments based on various evaluation criteria and with a set of additional annotations from third-party resources. The result is a comprehensive collection of information of crucial importance for human mitochondrial variation studies and investigation of common and rare diseases in which the mitochondrion may be involved. HmtVar is accessible at https://www.hmtvar.uniba.it and data may be retrieved using either a web interface through the Query page or a state-of-the-art API for programmatic access
The proliferative response of HT-29 human colon adenocarcinoma cells to bombesin-like peptides
No full textBombesin-like peptides (BLP) and their receptors are widely distributed throughout the intestine and are potential mitogens for gastrointestinal cancers. In this study we characterized the proliferation induced by BLP in the human adenocarcinoma cell line HT-29. The number of HT-29 cells, partially serum deprived (1% fetal bovine serum) for 48 h, was increased after 24 h of stimulation with bombesin, GRP, neuromedin B (NMB) and neuromedin C (NMC) ranging from 0.1 nM up to 1 muM. Reverse transcription polymerase chain reaction studies, revealed the presence of mRNA for NMB and for the GRP preferring receptor (GRP-R). mRNA for GRP, NMB preferring receptor (NMB-R) and bombesin receptor subtype 3 (BRS-3) were not detected. [D-Phe(6)]bombesin-(6-13)methyl ester (Al) and BIM-23127 (A2), are considered as inhibitors of binding to GRP-R and NMB-R, respectively. Surprisingly, A I and A2 stimulated the proliferation of HT-29 cells. Moreover, in the simultaneous presence of 1 muM Al and 0.1 muM GRP or 0.1 nM or 0.1 muM bombesin, inhibition of the proliferation was observed. Our data demonstrate that the proliferation induced by BLP in HT-29 cells is due to interaction with the GR-P-R. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved
A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma
Full text linkThe Von Hippel-Lindau (VHL) syndrome has been rarely associated with renal oncocytomas, and tumors usually show HIF1α chronic stabilization. By contrast, oncocytomas mainly associated with respiratory chain (RC) defects due to severe mitochondrial DNA (mtDNA) mutations are incapable of stabilizing HIF1α, since oxygen consumption by the RC is dramatically diminished and prolylhydroxylase activity is increased by α-ketoglutarate accumulation following Krebs cycle slowdown. Here, we investigate the cooccurrence of a pseudohypoxic condition with oncocytic transformation in a case of VHL-associated renal oncocytoma. While HIF1α was abundant in nuclei concordantly with defects in VHL, negative staining of its targets carbonic anhydrase IX (CAIX) and glucose transporter GLUT1, usually overexpressed in VHL-associated neoplasms, suggested HIF1α to be present in its inactive (hydroxylated) form. MtDNA sequencing and immunohistochemistry analyses revealed a MT-CO1 stop-gain mutation and cytochrome c oxidase loss. We suggest that a mitochondrial respiration impairment may lead to hyperhydroxylation of the transcription factor, which we confirmed by specific staining of hydroxylated HIF1α. Such inactive form hence accumulated in the VHL-deficient tumor, where it may contribute to the benign nature of the neoplasm. We propose that the protumorigenic role of HIF1α in VHL cancers may be blunted through drugs inhibiting mitochondrial respiratory complexes, such as metformin
The multifaceted effects of metformin on tumor microenvironment
Full text linkThe efficacy of metformin in treating cancer has been extensively investigated since epidemiologic studies associated this anti-diabetic drug with a lower risk of cancer incidence. Since tumors are complex systems, in which cancer cells coexist and interact with several different types of non-malignant cells, it is not surprising that anti-cancer drugs affect not only cancer cells, but also the abundance and functions of cells of the tumor microenvironment. Recent years have seen a wide collection of reports showing how metformin, as well as other complex I inhibitors, may influence cancer progression by modulating the phenotype of non-transformed cells in a tumor. In this review, we particularly focus on the effect of metformin on angiogenesis, cancer-associated fibroblasts, tumor-associated macrophages and cancer immunosuppression
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