Search

Human angiogenin (hANG) is the most studied stress-induced ribonuclease (RNase). In physiological conditions it performs its main functions in nucleoli, promoting cell proliferation by rDNA transcription, whereas it is strongly limited by its inhibitor (RNH1) throughout the rest of the cell. In stressed cells hANG dissociates from RNH1 and thickens in the cytoplasm where it manages the translational arrest and the recruitment of stress granules, thanks to its propensity to cleave tRNAs and to induce the release of active halves. Since it exists a clear connection between hANG roles and its intracellular routing, starting from our recent findings on heterologous ANG (ANG) properties in human keratinocytes (HaCaT cells), here we designed a variant unable to translocate into the nucleus with the aim of thoroughly verifying its potentialities under stress. This variant, widely characterized for its structural features and biological attitudes, shows more pronounced aid properties than unmodified protein. The collected evidence thus fully prove that ANG stress-induced skills in assisting cellular homeostasis are strictly due to its cytosolic localization. This study opens an interesting scenario for future studies regarding both the strengthening of skin defences and in understanding the mechanism of action of these special enzymes potentially suitable for any cell type.

Aberrant production of reactive oxygen species (ROS) from dysfunctional mitochondria leads to oxidative stress and DNA damage, which induces the cellular senescence stress response pathway. This, while exerting strong beneficial suppressive effects on the development of cancer, also contributes to aging and different age-related disorders. Mitophagy is a key mechanism to constantly eliminate old and damaged mitochondria, strongly contributing to keep low levels of intracellular ROS. Here, we discuss our recent findings showing the involvement of the atypical MAP kinase family member MAPK15 in controlling the mitophagic process, thereby preventing ROS accumulation, extensive DNA damage and activation of the cellular senescence phenotype.

The beneficial roles of resveratrol (RES) in affecting proliferation of multiple cancer cells have attracted intensive attention. However, the underlying mechanism remains unclear. This study aims to bridge the knowledge gap by investigating RES-induced growth inhibition of HeLa cells. Our work focuses on the metergasis of mitochondria in the RES-exposed cells. Therefore, HeLa cells were treated with different concentrations of RES for 30 min and 24 h, respectively. As a result, concentration-dependent increases in cell growth inhibition, ROS (reactive oxygen species) triggering, and LC3-II (light chain 3-II) expression were detected in the HeLa cells exposed to RES for 24 h. Interestingly, a specific concentration-dependent effect was observed in the HeLa cells exposed to RES for 30 min, that is, low concentration RES (≤ 25 μmol/L) reduced ROS levels, inhibited transcription and expression levels of LC3-II, and stimulated mitochondrial respiratory capacities. In contrast, high concentration RES (50 and 100 μmol/L) induced ROS over-production and autophagy in the cells, resulting in decreased levels of mitochondrial membrane potential, mitochondrial DNA copy numbers, and mitochondrial respiratory capacities. Together, our data concluded that RES inhibited HeLa cell proliferation through perturbation of mitochondrial structure and function, and ROS-induced autophagy also played a critical role in the process.

The voltage-gated calcium channels (CaVs or VGCCs) are fundamental regulators of intracellular calcium homeostasis. When electrical activity induces their activation, the influx of calcium that they mediate or their interaction with intracellular players leads to changes in intracellular Ca2+ levels which regulate many processes such as contraction, secretion and gene expression, depending on the cell type. The essential component of the pore channel is the CaVα1 subunit. However, the fine-tuning of Ca2+-dependent signals is guaranteed by the modulatory role of the auxiliary subunits β, α2δ, and γ of the CaVs. In particular, four different CaVβ proteins (CaVβ1, CaVβ2, CaVβ3, and CaVβ4) are encoded by four different genes in mammalians, each of them displaying several splice variants. Some of these isoforms have been described in regulating CaVα1 docking and stability at the membrane and controlling the channel complex’s conformational changes. In addition, emerging evidences have highlighted other properties of the CaVβ subunits, independently of α1 and non-correlated to its channel or voltage sensing functions. This review summarizes the recent findings reporting novel roles of the auxiliary CaVβ subunits and in particular their direct or indirect implication in regulating gene expression in different cellular contexts.

Preharvest application of hormetic doses of ultraviolet-C (UV-C) generates beneficial effects in plants. In this study, within 1 week, four UV-C treatments of 0.4 kJ/m2 were applied to 3-week-old lettuce seedlings. The leaves were inoculated with a virulent strain of Xanthomonas campestris pv. vitians (Xcv) 48 h after the last UV-C application. The extent of the disease was tracked over time and a transcriptomic analysis was performed on lettuce leaf samples. Samples of lettuce leaves, from both control and treated groups, were taken at two different times corresponding to T2, 48 h after the last UV-C treatment and T3, 24 h after inoculation (i.e., 72 h after the last UV-C treatment). A significant decrease in disease severity between the UV-C treated lettuce and the control was observed on days 4, 8, and 14 after pathogen inoculation. Data from the transcriptomic study revealed, that in response to the effect of UV-C alone and/or UV-C + Xcv, a total of 3828 genes were differentially regulated with fold change (|log2-FC|) > 1.5 and false discovery rate (FDR) < 0.05. Among these, of the 2270 genes of known function 1556 were upregulated and 714 were downregulated. A total of 10 candidate genes were verified by qPCR and were generally consistent with the transcriptomic results. The differentially expressed genes observed in lettuce under the conditions of the present study were associated with 14 different biological processes in the plant. These genes are involved in a series of metabolic pathways associated with the ability of lettuce treated with hormetic doses of UV-C to resume normal growth and to defend themselves against potential stressors. The results indicate that the hormetic dose of UV-C applied preharvest on lettuce in this study, can be considered as an eustress that does not interfere with the ability of the treated plants to carry on a set of key physiological processes namely: homeostasis, growth and defense.

Abstract: Antioxidant enzyme activity can be used to measure heat stress and predict the tolerance of a species to heat stress. This study investigated the effects of temperature on germination and antioxidant enzyme activity in Dalbergia spruceana Benth. seeds. Seeds were incubated at constant temperatures of 20, 25, 30, 35, and 40 °C for ten days; and germination percentage, germination speed index, antioxidant enzyme activity, and electrical conductivity were evaluated. Temperature affected the seed germination process but not antioxidant enzyme activity. Germination percentage and germination speed index were higher at 25 and 35 °C and lower at 20 and 40 °C. Superoxide dismutase activity was not affected by temperature. Catalase and peroxidase activities were too low to be used as indicators of temperature stress. The pattern of increasing electrolyte leakage manifested a trend toward loss of cell membrane semipermeability at higher temperatures.

Using a transcriptomic approach, we performed a pilot study in healthy subjects to evaluate the changes in gene expression induced by grape consumption. Blood from twenty subjects was collected at baseline (T0), after 21 days of grape-rich diet (T1) and after one-month washout (T2). Gene expression profiling of peripheral blood mononuclear cells from six subjects identified 930 differentially expressed transcripts. Gene functional analysis revealed changes (at T1 and/or T2) suggestive of antithrombotic and anti-inflammatory effects, confirming and extending previous finding on the same subjects. Moreover, we observed several other favourable changes in the transcription of genes involved in crucial processes such as immune response, DNA and protein repair, autophagy and mitochondrial biogenesis. Finally, we detected significant changes in many long non-coding RNAs genes, whose regulatory functions are being increasingly appreciated. Altogether, our data suggest that a grape diet may exert its beneficial effects by targeting different strategic pathways.

Phytocannabinoids are a structurally diverse class of bioactive naturally occurring compounds found in angiosperms, fungi, and liverworts and produced in several plant organs such as the flower and glandular trichrome of Cannabis sativa, the scales in Rhododendron, and oil bodies of liverworts such as Radula species; they show a diverse role in humans and plants. Moreover, phytocannabinoids are prenylated polyketides, i.e., terpenophenolics, which are derived from isoprenoid and fatty acid precursors. Additionally, targeted productions of active phytocannabinoids have beneficial properties via the genes involved and their expression in a heterologous host. Bioactive compounds show a remarkable non-hallucinogenic biological property that is determined by the variable nature of the side chain and prenyl group defined by the enzymes involved in their biosynthesis. Phytocannabinoids possess therapeutic, antibacterial, and antimicrobial properties; thus, they are used in treating several human diseases. This review gives the latest knowledge on their role in the amelioration of abiotic (heat, cold, and radiation) stress in plants. It also aims to provide synthetic and biotechnological approaches based on combinatorial biochemical and protein engineering to synthesize phytocannabinoids with enhanced properties.

The inflammation process represents of a dynamic series of phenomena that manifest themselves with an intense vascular reaction. Neuroinflammation is a reply from the central nervous system (CNS) and the peripheral nervous system (PNS) to a changed homeostasis. There are two cell systems that mediate this process: the glia of the CNS and the lymphocites, monocytes, and macrophages of the hematopoietic system. In both the peripheral and central nervous systems, neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases, and in neuropsychiatric illnesses, such as depression and autism spectrum disorders. The resolution of neuroinflammation is a process that allows for inflamed tissues to return to homeostasis. In this process the important players are represented by lipid mediators. Among the naturally occurring lipid signaling molecules, a prominent role is played by the N-acylethanolamines, namely N-arachidonoylethanolamine and its congener N-palmitoylethanolamine, which is also named palmitoylethanolamide or PEA. PEA possesses a powerful neuroprotective and anti-inflammatory power but has no antioxidant effects per se. For this reason, its co-ultramicronization with the flavonoid luteolin is more efficacious than either molecule alone. Inhibiting or modulating the enzymatic breakdown of PEA represents a complementary therapeutic approach to treating neuroinflammation. The aim of this review is to discuss the role of ultramicronized PEA and co-ultramicronized PEA with luteolin in several neurological diseases using preclinical and clinical approaches.