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MPP+ is the active metabolite of MPTP, a molecule structurally similar to the herbicide Paraquat, known to injure the dopaminergic neurons of the nigrostriatal system in Parkinson's disease models. Within the cells, MPP+ accumulates in mitochondria where it inhibits complex I of the electron transport chain, resulting in ATP depletion and neuronal impairment/death. So far, MPP+ is recognized as a valuable tool to mimic dopaminergic degeneration in various cell lines. However, despite a large number of studies, a detailed characterization of mitochondrial respiration in neuronal cells upon MPP+ treatment is still missing. By using high-resolution respirometry, we deeply investigated oxygen consumption related to each respiratory state in differentiated neuroblastoma cells exposed to the neurotoxin. Our results indicated the presence of extended mitochondrial damage at the inner membrane level, supported by increased LEAK respiration, and a drastic drop in oxygen flow devoted to ADP phosphorylation in respirometry measurements. Furthermore, prior to complex I inhibition, an enhancement of complex II activity was observed, suggesting the occurrence of some compensatory effect. Overall our findings provide a mechanistic insight on the mitochondrial toxicity mediated by MPP+, relevant for the standardization of studies that employ this neurotoxin as a disease model. [ABSTRACT FROM AUTHOR]

Background: A positive correlation between calcium and magnesium serum levels is well known and depends upon various factors. This study aims at verifying the existence of this association in a retrospective series of patients who underwent thyroid surgery., Methods: Two hundred and eighty-five consecutive patients (202 female, 83 male, mean age 57 years) who underwent at least total thyroidectomy (TT) and had a complete clinical and biochemical pre- and postoperative evaluation were included in the study. Patients were evaluated with regard to: sex, age, indications for surgery, operative time, number of accidentally removed parathyroids, extent and time of surgery, thyroiditis, final histology, pre- and postoperative levels of calcium, magnesium, vitamin D, and creatinine, presence of symptoms of hypocalcemia. Statistical analysis was performed using the R software., Results: In the postoperative period, biochemical hypocalcemia (<8.5 mg/dL) was observed in 126 patients (44%) and severe hypocalcemia (<7.5 mg/dL, a level indicating the need for longer hospitalization) was seen in 40 (14%). When analyzing patients with and without postoperative hypocalcemia, the factors affecting postoperative biochemical hypocalcemia were: older age (P=0.019), longer operative time (P=0.039), and a highly significant correlation between postoperative calcium and magnesium levels (r=0.432; P<0.001)., Conclusions: The only factor among the ones we analyzed in this retrospective study that would appear to be linked to the onset of clinically relevant hypocalcemia is low magnesium levels in the postoperative period. A prospective randomized study with a group of patients undergoing magnesium replacement in the postoperative period can clarify the possible role of magnesium repletion on hypocalcemia.

Background: VDAC (Voltage-Dependent Anion selective Channel) is a small family of abundant pore-forming proteins located in the outer mitochondrial membrane. Their role range from the most intuitive, the formation of a hydrophilic conduit through the membrane thanks to its beta-barrel structure, to less understood functions that make them essential actors in the cross-talk between the bioenergetics metabolism and the cytosol components. Due to this localization, VDAC1, in particular, has been reported to be involved in apoptosis, Hexokinase and tubulin binding, and in the Warburg effect. For these reasons, an involvement of VDAC in cancer is considered consequential and a number of compounds have been proposed and used in experimental trials to demonstrate the efficacy of molecules affecting the functions of VDAC., Objectives: In this work, we thus survey the literature describing drug compounds acting on the cancerous proliferation through VDAC. Three main categories have been assigned: molecules acting on the VDAC-Hexokinase binding, molecules directly inhibiting the VDAC conductance, molecules affecting the expression levels of the VDAC gene. The application of biological peptides for this purpose is also considered., Conclusion: Since the knowledges about the functional properties of VDAC protein are still insufficient, VDAC as a pharmacological target in the fight against cancer is still a very open, but very promising, field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

VDACs (voltage-dependent anion-selective channels) or mitochondrial PORINS are transmembrane proteins forming pores in the outer membrane. In eukaryotic genomes multiple genes coding for VDAC homologues have been discovered, but the functional meaning of this gene redundancy is unknown. In Drosophila melanogasterthree additional genes homologous to the gene porin (CG6647) have been found. As in other occurences, the presence of a gene revealed by genome analysis raises the questions: are these genes really expressed? What are the molecular features of the putative proteins, if they are expressed? Where and when in the organism are they expressed? Consequently have they any specific activity justifying the presence of more isoforms in the organism? To answer to these questions we have produced antibodies against the recombinant proteins corresponding to the whole (VDAC1 and 2) or to substantial portions (VDAC3 and 4) of the known or predicted proteins. Immunohistological and transcriptional analysis has been performed, showing that VDAC2 and 3 are expressed, while VDAC4 was not detected. Structural predictions of VDAC3 are consistent with the presence of additional alpha-helices at the N-terminus of the protein.