Structural basis for catalysis and selectivity of phospholipid synthesis by eukaryotic choline-phosphotransferase.

Phospholipids are the most abundant component in lipid membranes and are essential for the structural and functional integrity of the cell. In eukaryotic cells, phospholipids are primarily synthesized de novo through the Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group of cytidine-5'-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) that use 1,2-diacylglycerol (DAG) and CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC) or phosphatidylethanolamine (PE) that are the main phospholipids in eukaryotic cells.

The relationship between muscle sympathetic nerve activity and serum fatty acid binding protein 4 at rest and during isometric handgrip exercise.

Fatty acid binding protein 4 (FABP4) is highly expressed in adipocytes. Lipolysis, caused by an elevated adrenergic input, has been suggested to contribute to elevated serum FABP4 levels in patients with cardiovascular diseases. However, the relationship between the serum FABP4 and efferent sympathetic nerve activity remains poorly understood.

Molecular alterations associated with pathophysiology in liver-specific ZO-1 and ZO-2 knockout mice.

The liver is a complex organ with a highly organized structure in which tight junctions (TJs) play an important role in maintaining their function by regulating barrier properties and cellular polarity. Dysfunction of TJs is associated with liver diseases, including progressive familial intrahepatic cholestasis (PFIC). In this study, we investigated the molecular alterations in a liver-specific ZO-1 and ZO-2 double-knockout (DKO) mouse model, which exhibits features resembling those of PFIC4 patients with mutations in the ZO-2 gene.

Structural reconstruction of mouse acute aortic dissection by intravenously administered human Muse cells without immunosuppression.

Background: Stanford type B-acute aortic dissection (type B-AAD) is often life-threatening without invasive surgery. Multilineage-differentiating stress enduring cell (Muse cells), which comprise several percent of mesenchymal stem cells (MSCs), are endogenous pluripotent-like stem cells that selectively home to damaged tissue and replace damaged/apoptotic cells by in-vivo differentiation.

Methods: Mortality, aortic diameter expansion, cell localization, cell differentiation, and inflammation of the dissected aorta were evaluated in type B-AAD model mice intravenously injected with human-Muse cells, -elastin-knockdown (KD)-Muse cells, -human leukocyte antigen-G (HLA-G)-KD-Muse cells, or MSCs, all without immunosuppressant.

Copulation Duration and Sperm Precedence with Reference to Larval Diapause Induction in Hope (Coleoptera: Cerambycidae).

Adults of the pine sawyer are the primary vector of , the causative agent of pine wilt disease. A sawyer subspecies in Taiwan (abbreviated 'T') has two generations a year (bivoltinism) due to facultative diapause, whereas another subspecies in Japan (abbreviated 'J') has a one- or two-year life cycle due to obligate diapause. T, with two infection periods a year, will cause more severe disease epidemics than J if it is introduced into Japan.

Autophagy inhibition suppresses hormone production and cell growth in pituitary tumor cells: A potential approach to pituitary tumors.

Pituitary tumors (PTs) represent about 10% of all intracranial tumors, and most are benign. However, some PTs exhibit continued growth despite multimodal therapies. Although temozolomide (TMZ), an alkylating chemotherapeutic agent, is a first-line medical treatment for aggressive PTs, some PTs are resistant to TMZ.

The ceramide transport protein CERT is involved in alkylacylglycerol transfer from the ER to the Golgi for the biosynthesis of ether phospholipid.

Ether phospholipids are synthesized by a series of enzymes localized in peroxisomes, the endoplasmic reticulum (ER), and the Golgi apparatus. During this process, the lipid intermediate alkylacylglycerol (AAG) synthesized in the ER is transferred from the site of its synthesis to the Golgi apparatus. In this study, we determined whether ceramide transport protein (CERT) is a candidate for AAG transfer.

Nuclear corepressor SMRT acts as a strong regulator of both β-oxidation and suppressor of fibrosis in the differentiation process of mouse skeletal muscle cells.

Background: Silencing Mediator of Retinoid and Thyroid hormone receptors (SMRT; NCoR2) is a transcriptional corepressor (CoR) which has been recognized as an important player in the regulation of hepatic lipogenesis and in somatic development in mouse embryo. SMRT protein is also widely expressed in mouse connective tissues, for example adipocytes and muscle. We recently reported that mice with global deletion of SMRT develop significant obesity and muscle wasting which are independent from thyroid hormone (TH) signaling and thermogenesis.

Effect of pulmonary vein isolation on the relationship between left atrial reverse remodeling and sympathetic nerve activity in patients with atrial fibrillation.

Purpose: Catheter ablation (CA) to isolate the pulmonary vein, which is an established treatment for atrial fibrillation (AF), is associated with left atrium reverse remodeling (LARR). The intrinsic cardiac autonomic nervous system includes the ganglion plexi adjacent to the pulmonary vein in the left atrium (LA). However, little is known about the effect of CA on the relationship between LARR and sympathetic nerve activity in patients with AF.

Relationships between muscle sympathetic nerve activity and novel indices of arterial stiffness using single oscillometric cuff in patients with hypertension.

The arterial velocity pulse index (AVI) and arterial pressure-volume index (API) have been proposed as new arterial stiffness indices that can be measured using an oscillometric cuff. Sympathetic nerve activity (SNA) contributes to arterial stiffness via increasing vascular smooth muscle tone. However, the associations between SNA and the AVI or API are not understood.

Metabolic changes induced by TGF-β1 via reduced expression of phosphatidylserine decarboxylase during myofibroblast transition.

Metabolic alteration is increasingly recognized as an important pathogenic process that underlies fibrosis across many organ types, and metabolically targeted therapies could become important strategies for reducing fibrosis. In present study, target enzymes that are involved in changes in phospholipid metabolism during fibroblast-to-myofibroblast transition induced by transforming growth factor beta 1 (TGF-β1) were examined. Different amounts of phospholipids were found in the 2 groups.

Transcription of cytochrome P450 46A1 in NIH3T3 cells is negatively regulated by FBS.

Extracellular administration of side-chain oxysterols, such as 24S-hydroxycholesterol (24S-HC), 27-hydroxycholesterol (27-HC) and 25-hydroxycholesterol (25-HC) to cells suppresses HMG-CoA reductase (Hmgcr) and CTP:phosphoethanolamine cytidylyltransferase (Pcyt2) mRNA levels. Oxysterols are enzymatically produced in cells from cholesterol by cytochrome P450 46A1 (Cyp46A1), Cyp27A1, Cyp3A11 and cholesterol 25-hydroxylase (Ch25h). We analyzed which of these oxysterol-producing enzymes are expressed in NIH3T3 cells and found that only Cyp46A1 was expressed.

Different Responses of Muscle Sympathetic Nerve Activity to Dapagliflozin Between Patients With Type 2 Diabetes With and Without Heart Failure.

Background Sodium-glucose cotransporter 2 inhibitors improve cardiovascular outcomes in patients with diabetes with and without heart failure (HF). However, their influence on sympathetic nerve activity (SNA) remains unclear. The purpose of this study was to evaluate the effect of sodium-glucose cotransporter 2 inhibitors on SNA and compare the responses of SNA to sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes with and without HF.

Differential contributions of choline phosphotransferases CPT1 and CEPT1 to the biosynthesis of choline phospholipids.

Choline phospholipids (PLs) such as phosphatidylcholine (PC) and 1-alkyl-2-acyl-sn-glycerophosphocholine are important components for cell membranes and also serve as a source of several lipid mediators. These lipids are biosynthesized in mammals in the final step of the CDP-choline pathway by the choline phosphotransferases choline phosphotransferase 1 (CPT1) and choline/ethanolamine phosphotransferase 1 (CEPT1). However, the contributions of these enzymes to the de novo biosynthesis of lipids remain unknown.

The zonula occludens protein family regulates the hepatic barrier system in the murine liver.

The hepatic barrier is indispensable for the physiological functions of the liver and is impaired under various pathological conditions. Tight junctions reportedly play a central role in hepatic barrier regulation; however, there is limited direct evidence supporting this observation, with few in vivo models or confirmations of the implicated molecular mechanisms presented to date. We inactivated the tight junction component gene, Tjp2/ZO-2, and the related molecule, Tjp1/ZO-1, in mouse livers.

Different prognosis between severe and very severe obstructive sleep apnea patients; Five year outcomes.

Background: Obstructive sleep apnea (OSA) is characterized by augmented sympathetic nerve activity. In our previous study, patients with OSA and an apnea-hyperpnea index (AHI)>55events/h showed increased single-unit muscle sympathetic nerve activity compared to patients with OSA and AHI of 30-55events/h. However, the prognostic impact in these patients remains unclear.

L-type amino acid transporter 1, LAT1, in growth hormone-producing pituitary tumor cells.

Pituitary tumors (PTs) can cause significant mortality and morbidity due to limited therapeutic options. L-type amino acid transporters (LATs), in particular, the LAT1 isoform, is expressed in a variety of tumor cells. Pharmacological inhibition or genetic ablation of LAT1 can suppress leucine transport into cancer cells, resulting in suppression of cancer cell growth.

Locations and contributions of the phosphotransferases EPT1 and CEPT1 to the biosynthesis of ethanolamine phospholipids.

The final step of the CDP-ethanolamine pathway is catalyzed by ethanolamine phosphotransferase 1 (EPT1) and choline/EPT1 (CEPT1). These enzymes are likely involved in the transfer of ethanolamine phosphate from CDP-ethanolamine to lipid acceptors such as 1,2-diacylglycerol (DAG) for PE production and 1-alkyl-2-acyl-glycerol (AAG) for the generation of 1-alkyl-2-acyl-glycerophosphoethanolamine. Here, we investigated the intracellular location and contribution to ethanolamine phospholipid (EP) biosynthesis of EPT1 and CEPT1 in HEK293 cells.

Imaging of lysophosphatidylcholine in an induced pluripotent stem cell-derived endothelial cell network.

Introduction: Vascular endothelial cell disorders are closely related to cardiovascular disease (CVD) and pulmonary diseases. Abnormal lipid metabolism in the endothelium leads to changes in cell signalling, and the expression of genes related to immunity and inflammation. It is therefore important to investigate the pathophysiology of vascular endothelial disorders in terms of lipid metabolism, using a disease model of endothelium.

Renal iodine-metaiodobenzylguanidine scintigraphy relates to muscle sympathetic nervous activity in heart failure with reduced ejection fraction.

Background: Renal denervation is effective for modulating augmented sympathetic nerve activity (SNA) in heart failure with reduced ejection fraction (HFrEF). We have demonstrated that renal iodine-metaiodobenzylguanidine (I-MIBG) scintigraphy is associated with muscle sympathetic nerve activity (MSNA) in patients with hypertension. However, it is unclear whether renal I-MIBG scintigraphy is useful for assessment of SNA in HFrEF.

The phosphatidylcholine transfer protein StarD7 is important for myogenic differentiation in mouse myoblast C2C12 cells and human primary skeletal myoblasts.

StarD7 is a phosphatidylcholine (PC)-specific lipid transfer protein essential for the maintenance of mitochondrial PC composition, morphogenesis, and respiration. Here, we studied the role of StarD7 in skeletal myoblast differentiation using mouse myoblast C2C12 cells and human primary myoblasts. Immunofluorescence and immuno-electron microscopy revealed that StarD7 was distributed in the cytosol, inner mitochondria space, and outer leaflet of the outer mitochondrial membrane in C2C12 cells.

Characterization of glycerophosphodiesterase 4-interacting molecules Gαq/11 and Gβ, which mediate cellular lysophospholipase D activity.

We previously purified lysophospholipase D (lysoPLD), which hydrolyzes lysophosphatidylcholine (lysoPC) to lysophosphatidic acid (LPA), from rat brain and identified the heterotrimeric G protein subunits Gαq and Gβ1 in the lysoPLD active fractions. Tag-affinity purified Gαq exhibits lysoPLD activity but a mutant that affected cellular localization or interaction with the Gβ subunit reduced lysoPLD activity. Size exclusion chromatography revealed that active lysoPLD is a much higher molecular mass complex than is heterotrimeric G protein, suggesting the presence of other components.