The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion.

Background: Cerebral vascular protection is critical for stroke treatment. Adenosine modulates vascular flow and exhibits neuroprotective effects, in which brain extracellular concentration of adenosine is dramatically increased during ischemic events and ischemia-reperfusion. Since the equilibrative nucleoside transporter-2 (Ent2) is important in regulating brain adenosine homeostasis, the present study aimed to investigate the role of Ent2 in mice with cerebral ischemia-reperfusion.

Predictors of Response to Oral Medications and Low-Histamine Diet in Patients with Chronic Urticaria.

Background: Chronic urticaria (CU) is comprised of diverse phenotypes, and thus, a shift towards a precision medical approach is warranted in its management.

Methods: This study enrolled 78 patients with CU. Serum erythrocyte sedimentation rate, hemoglobin, hematocrit, eosinophil count, IgE, antinuclear antibody (ANA), and serum diamine oxidase (DAO) levels of the patients were measured and were compared according to the patient's response to second-generation antihistamines (sgAH), corticosteroids, leukotriene receptor antagonist (LTRA), H blockers, and low-histamine diet.

Intracellular vesicle clusters are organelles that synthesize extracellular vesicle-associated cargo proteins in yeast.

Extracellular vesicles (EVs) play important roles in cell-cell communication. In budding yeast (), EVs function as carriers to transport cargo proteins into the periplasm for storage during glucose starvation. However, intracellular organelles that synthesize these EV-associated cargo proteins have not been identified.

Which Fruits and Vegetables Should Be Excluded from a Low-Salicylate Diet? An Analysis of Salicylic Acid in Foodstuffs in Taiwan.

Background: Eliminating pseudoallergens is an important element of managing chronic spontaneous urticaria (CSU). Salicylic acid (SA) is a primary pseudoallergen in plant-based foodstuffs. Current dietary recommendations are not applicable in East Asia because data on the SA content of many vegetables and fruits commonly consumed in this region are lacking.

The Shape of Vesicle-Containing Organelles Is Critical for Their Functions in Vesicle Endocytosis.

Exosomes are small vesicles secreted by a variety of cell types under physiological and pathological conditions. When Saccharomyces cerevisiae are grown in low glucose, small vesicles carrying more than 300 proteins with diverse biological functions are secreted. Upon glucose addition, secreted vesicles are endocytosed that requires cup-shaped organelles containing the major eisosome protein Pil1p at the rims.

Vps15p regulates the distribution of cup-shaped organelles containing the major eisosome protein Pil1p to the extracellular fraction required for endocytosis of extracellular vesicles carrying metabolic enzymes.

Background Information: Exosomes are small vesicles secreted from virtually every cell from bacteria to humans. Saccharomyces cerevisiae is a model system to study trafficking of small vesicles in response to changes in the environment. When yeast cells are grown in low glucose, vesicles carrying gluconeogenic enzymes are present as free vesicles and aggregated clusters in the cytoplasm.

Yeast as a Model System to Study Trafficking of Small Vesicles Carrying Signal-less Proteins In and Out of the Cell.

Exosomes are small vesicles that are released from a variety of cells and are involved in cell-to-cell communication. In humans, exosomes are detected in the plasma, urine, saliva, and cerebrospinal fluid. These vesicles carry multiple cargo proteins, as well as microRNA that affect the transcription of target genes.

Exocytosis and Endocytosis of Small Vesicles across the Plasma Membrane in Saccharomyces cerevisiae.

When Saccharomyces cerevisiae is starved of glucose, the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase, isocitrate lyase, and malate dehydrogenase, as well as the non-gluconeogenic enzymes glyceraldehyde-3-phosphate dehydrogenase and cyclophilin A, are secreted into the periplasm. In the extracellular fraction, these secreted proteins are associated with small vesicles that account for more than 90% of the total number of extracellular structures observed. When glucose is added to glucose-starved cells, FBPase is internalized and associated with clusters of small vesicles in the cytoplasm.

The endocytosis gene END3 is essential for the glucose-induced rapid decline of small vesicles in the extracellular fraction in Saccharomyces cerevisiae.

Background: Protein secretion is a fundamental process in all living cells. Gluconeogenic enzymes are secreted when Saccharomyces cerevisiae are grown in media containing low glucose. However, when cells are transferred to media containing high glucose, they are internalized.

Fructose-1,6-bisphosphatase, Malate Dehydrogenase, Isocitrate Lyase, Phosphoenolpyruvate Carboxykinase, Glyceraldehyde-3-phosphate Dehydrogenase, and Cyclophilin A are secreted in Saccharomyces cerevisiae grown in low glucose.

Our previous studies demonstrated that the key gluconeogenic enzyme fructose-1,6-bisphosphatase is secreted when Saccharomyces cerevisiae are starved of glucose for a prolonged period of time. In this study, we showed that malate dehydrogenase, isocitrate lyase, phosphoenolpyruvate carboxykinase, glyceraldehyde-3-phosphate dehydrogenase, and cyclophilin A are also secreted in glucose-starved cells. Thus, both gluconeogenic and non-gluconeogenic enzymes are secreted via the non-classical pathway.

Glucose induces rapid changes in the secretome of Saccharomyces cerevisiae.

Background: Protein secretion is a fundamental process in all living cells. Proteins can either be secreted via the classical or non-classical pathways. In Saccharomyces cerevisiae, gluconeogenic enzymes are in the extracellular fraction/periplasm when cells are grown in media containing low glucose.

The key gluconeogenic enzyme fructose-1,6-bisphosphatase is secreted during prolonged glucose starvation and is internalized following glucose re-feeding via the non-classical secretory and internalizing pathways in Saccharomyces cerevisiae.

In Saccharomyces cerevisia, the key gluconeogenic enzyme fructose-1,6-bisphosphatase is secreted into the periplasm during prolonged glucose starvation and is internalized into Vid/endosomes following glucose re-feeding. Fructose-1,6-bisphosphatase does not contain signal sequences required for the classical secretory and endocytic pathways. Hence, the secretion and internalization are mediated via the non-classical pathways.

Vid28 protein is required for the association of vacuole import and degradation (Vid) vesicles with actin patches and the retention of Vid vesicle proteins in the intracellular fraction.

Gluconeogenic enzymes are induced when Saccharomyces cerevisiae are starved of glucose. However, when glucose is added to prolonged starved cells, these enzymes are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. The Vid pathway is linked to the nonclassical secretory and internalizing pathways.

Guidelines for the use and interpretation of assays for monitoring autophagy.

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding.

Vps34p is required for the decline of extracellular fructose-1,6-bisphosphatase in the vacuole import and degradation pathway.

When Saccharomyces cerevisiae are starved of glucose for a prolonged period of time, gluconeogenic enzymes such as fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase, isocitrate lyase, and phosphoenolpyruvate carboxykinase are induced. However, when glucose is added to prolonged-starved cells, these enzymes are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. The Vid pathway merges with the endocytic pathway to remove intracellular and extracellular proteins simultaneously.

Comparative proteomic analysis of transition of saccharomyces cerevisiae from glucose-deficient medium to glucose-rich medium.

Background: When glucose is added to Saccharomyces cerevisiae grown in non-fermentable carbon sources, genes encoding ribosomal, cell-cycle, and glycolytic proteins are induced. By contrast, genes involved in mitochondrial functions, gluconeogenesis, and the utilization of other carbon sources are repressed. Glucose also causes the activation of the plasma membrane ATPase and the inactivation of gluconeogenic enzymes and mitochondrial enzymes.

Vacuole import and degradation pathway: Insights into a specialized autophagy pathway.

Glucose deprivation induces the synthesis of pivotal gluconeogenic enzymes such as fructose-1,6-bisphosphatase, malate dehydrogenase, phosphoenolpyruvate carboxykinase and isocitrate lyase in Saccharomyces cerevisiae. However, following glucose replenishment, these gluconeogenic enzymes are inactivated and degraded. Studies have characterized the mechanisms by which these enzymes are inactivated in response to glucose.

Vid30 is required for the association of Vid vesicles and actin patches in the vacuole import and degradation pathway.

When Saccharomyces cerevisiae is starved of glucose, the gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase (MDH2), isocitrate lyase (Icl1) and phosphoenolpyruvate carboxykinase (Pck1) are induced. However, when glucose is added to prolonged starved cells, these enzymes are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. Recent evidence suggests that the Vid pathway merges with the endocytic pathway at actin patches where endocytic vesicles are formed.

The TOR complex 1 is required for the interaction of multiple cargo proteins selected for the vacuole import and degradation pathway.

Upon starving Saccharomyces cerevisiae of glucose, the key gluconeogenic enzymes fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase (MDH2), isocitrate lyase (Icl1p) and phosphoenolpyruvate carboxykinase (Pck1p) are induced. When glucose is added to cells that have been starved for 3 days, these gluconeogenic enzymes are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. Moreover, it has been determined that during glucose starvation, these cargo proteins interact with the target of rapamycin complex 1 (TORC1), which is comprised of Tor1p, Tco89p, Lst8p and Kog1p.

The TOR complex 1 is distributed in endosomes and in retrograde vesicles that form from the vacuole membrane and plays an important role in the vacuole import and degradation pathway.

The key gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase) is induced when Saccharomyces cerevisiae are starved of glucose. However, when glucose is added to cells that have been starved for 3 days, FBPase is degraded in the vacuole. FBPase is first imported to Vid (vacuole import and degradation) vesicles, and these vesicles then merge with the endocytic pathway.

The vacuole import and degradation pathway utilizes early steps of endocytosis and actin polymerization to deliver cargo proteins to the vacuole for degradation.

When glucose is added to yeast cells that are starved for 3 days, fructose-1,6-bisphosphatase (FBPase) and malate dehydrogenase 2 are degraded in the vacuole via the vacuole import and degradation (Vid) pathway. In this study, we examined the distribution of FBPase at the ultrastructural level. FBPase was observed in areas close to the plasma membrane and in cytoplasmic structures that are heterogeneous in size and density.

A selective autophagy pathway that degrades gluconeogenic enzymes during catabolite inactivation.

In Saccharomyces cerevisiae, glucose starvation induces key gluconeogenic enzymes such as fructose-1,6-bisphosphatase (FBPase), malate dehydrogenase (MDH2) and phosphoenolpyruvate carboxykinase, while glucose addition inactivates these enzymes. Significant progress has been made identifying mechanisms that mediate the "catabolite inactivation" of FBPase and MDH2. For example, the site of their degradation has been shown to change, depending on the duration of starvation.

The vacuolar import and degradation pathway merges with the endocytic pathway to deliver fructose-1,6-bisphosphatase to the vacuole for degradation.

The gluconeogenic enzyme fructose-1,6-bisphosphatase (FBPase) is degraded in the vacuole when glucose is added to glucose-starved cells. Before it is delivered to the vacuole, however, FBPase is imported into intermediate carriers called Vid (vacuole import and degradation) vesicles. Here, using biochemical and genetic approaches, we identified a requirement for SEC28 in FBPase degradation.