Disulfide cross-linking of subunits F1-γ and F0I-PVP(b) results in asymmetric effects on proton translocation in the mitochondrial ATP synthase.

AbstractA study is presented on the effect of diamide-induced disulfide cross-linking of F1-γ and F0I-PVP(b) subunits on proton translocation in the mitochondrial ATP synthase. The results show that, upon cross-linking of these subunits, whilst proton translocation from the A side to the B F1 side is markedly accelerated with decoupling of oxidative phosphorylation, proton translocation in the reverse direction, driven by either ATP hydrolysis or a diffusion potential, is unaffected. These observations reveal further peculiarities of the mechanism of energy transfer in the ATP synthase of coupling membranes

Beneficial Oxidative Stress-Related trans-Resveratrol Effects in the Treatment and Prevention of Breast Cancer

Resveratrol is one of the most investigated polyphenols for its multiple biological activities and many beneficial effects. These are mainly related to its ability to scavenge free radicals and reduce oxidative stress. Resveratrol has also been shown to have the ability to stimulate the production of antioxidant enzymes, which interact with numerous signaling pathways involved in tumor development, and to possess side effects associated with the use of chemotherapy drugs. In this review article we summarized the main discoveries about the impact resveratrol can have in helping to prevent, as well as adjuvant treating, breast cancer. A brief overview of the primary sources of resveratrol as well as some approaches for improving its bioavailability have been also discussed

Poly(l-lactide-co-caprolactone-co-glycolide)-based nanoparticles as delivery platform: effect of the surfactants on characteristics and delivery efficiency

Polymeric nanoparticles made of the copolymer Poly(L-lactide-co-caprolactone-co-glycolide) were prepared using the solvent evaporation method. Two different surfactants, polyvinyl alcohol and dextran, and a mixture of the two were employed. The three types of nanoparticles were used as hosting carriers of two chemotherapeutic drugs, the hydrophilic doxorubicin and the hydrophobic SN-38. The morphostructural characterization showed similar features for the three types of nanoparticles, while the drug encapsulation efficiency indicated that the dextran-based systems are the most effective with both drugs. Cellular studies with breast cancer cells were performed to compare the delivery capability and the cytotoxicity profile of the three nanosystems. The results show that the unloaded nanoparticles are highly biocompatible at the administered concentrations and confirmed that dextran-coated nanoparticles are the most efficient vectors to release the two drugs, exerting cytotoxic activity. PVA, on the other hand, shows limited drug release in vitro, probably due to strong interactions with both drugs. Data also show the release is more efficient for doxorubicin than for SN-38; indeed, the doxorubicin IC50 value for the dextran-coated nanoparticles was about 35% lower than the free drug. This indicates that these nanocarriers are suitable candidates to deliver hydrophilic drugs while needing further modification to host hydrophobic molecules.info:eu-repo/semantics/publishedVersio

Polymeric nano-micelles as novel cargo-carriers for LY2157299 liver cancer cells delivery

LY2157299 (LY), which is very small molecule bringing high cancer diffusion, is a pathway antagonist against TGF\u3b2. LY dosage can be diluted by blood plasma, can be captured by immune system or it might be dissolved during digestion in gastrointestinal tract. The aim of our study is to optimize a "nano-elastic" carrier to avoid acidic pH of gastrointestinal tract, colon alkaline pH, and anti-immune recognition. Polygalacturonic acid (PgA) is not degradable in the gastrointestinal tract due to its insolubility at acidic pH. To avoid PgA solubility in the colon, we have designed its conjugation with Polyacrylic acid (PAA). PgA-PAA conjugation has enhanced their potential use for oral and injected dosage. Following these pre-requisites, novel polymeric nano-micelles derived from PgA-PAA conjugation and loading LY2157299 are developed and characterized. Efficacy, uptake and targeting against a hepatocellular carcinoma cell line (HLF) have also been demonstrated.LY2157299 (LY), which is very small molecule bringing high cancer diffusion, is a pathway antagonist against TGF\uce\ub2. LY dosage can be diluted by blood plasma, can be captured by immune system or it might be dissolved during digestion in gastrointestinal tract. The aim of our study is to optimize a \ue2\u80\u9cnano-elastic\ue2\u80\u9d carrier to avoid acidic pH of gastrointestinal tract, colon alkaline pH, and anti-immune recognition. Polygalacturonic acid (PgA) is not degradable in the gastrointestinal tract due to its insolubility at acidic pH. To avoid PgA solubility in the colon, we have designed its conjugation with Polyacrylic acid (PAA). PgA-PAA conjugation has enhanced their potential use for oral and injected dosage. Following these pre-requisites, novel polymeric nano-micelles derived from PgA-PAA conjugation and loading LY2157299 are developed and characterized. Efficacy, uptake and targeting against a hepatocellular carcinoma cell line (HLF) have also been demonstrated

Effect of resveratrol on mitochondrial function: Implications in parkin-associated familiar Parkinson's disease

Mitochondrial dysfunction and oxidative stress occur in Parkinson's disease (PD), but the molecular mechanisms controlling these events are not completely understood. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a transcriptional coactivator known as master regulator of mitochondrial functions and oxidative metabolism. Recent studies, including one from our group, have highlighted altered PGC-1α activity and transcriptional deregulation of its target genes in PD pathogenesis suggesting it as a new potential therapeutic target. Resveratrol, a natural polyphenolic compound proved to improve mitochondrial activity through the activation of several metabolic sensors resulting in PGC-1α activation. Here we have tested in vitro the effect of resveratrol treatment on primary fibroblast cultures from two patients with early-onset PD linked to different Park2 mutations. We show that resveratrol regulates energy homeostasis through activation of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1) and raise of mRNA expression of a number of PGC-1α's target genes resulting in enhanced mitochondrial oxidative function, likely related to a decrease of oxidative stress and to an increase of mitochondrial biogenesis. The functional impact of resveratrol treatment encompassed an increase of complex I and citrate synthase activities, basal oxygen consumption, and mitochondrial ATP production and a decrease in lactate content, thus supporting a switch from glycolytic to oxidative metabolism. Moreover, resveratrol treatment caused an enhanced macro-autophagic flux through activation of an LC3-independent pathway. Our results, obtained in early-onset PD fibroblasts, suggest that resveratrol may have potential clinical application in selected cases of PD-affected patients

Neuroprotective Investigation of Chitosan Nanoparticles for Dopamine Delivery

Chitosan nanoparticles (CS NPs) have been widely exploited for the delivery of various types of drugs due to their biocompatibility, availability, ease of functionalization and other advantages. Nevertheless, despite their wide use, their mechanism of action is not very clear and many aspects still need to be investigated in detail, with only a few studies having studied the behavior of this polymer. We prepared CS NPs encapsulating dopamine (DA) and studied the generation of reactive oxygen species (ROS) and the antioxidant effect of the neurotransmitter in detail. Encapsulation of the drug and its subsequent sustained release significantly reduced the oxidation rate in vitro, thus potentially exerting neuroprotective effects. ROS production in SH-SY5Y cells was investigated through a H2O2 assay, while a deeper study of the enzymatic activity allowed us to determine the significant contribution of both GPx and SOD enzymes in preventing oxidative stress

Neuroprotective Investigation of Chitosan Nanoparticles for Dopamine Delivery

Chitosan nanoparticles (CS NPs) have been widely exploited for the delivery of various types of drugs due to their biocompatibility, availability, ease of functionalization and other advantages. Nevertheless, despite their wide use, their mechanism of action is not very clear and many aspects still need to be investigated in detail, with only a few studies having studied the behavior of this polymer. We prepared CS NPs encapsulating dopamine (DA) and studied the generation of reactive oxygen species (ROS) and the antioxidant effect of the neurotransmitter in detail. Encapsulation of the drug and its subsequent sustained release significantly reduced the oxidation rate in vitro, thus potentially exerting neuroprotective effects. ROS production in SH-SY5Y cells was investigated through a H2O2 assay, while a deeper study of the enzymatic activity allowed us to determine the significant contribution of both GPx and SOD enzymes in preventing oxidative stress