Phosphatidic acid

OBJECTIVE: To investigate the alterations in serum metabolic profiles and early-stage hepatocellular carcinoma (HCC) patient characteristics after radiofrequency ablation (RFA) therapy. This evaluation aimed to assess treatment effectiveness and identify potential novel approaches and targets for HCC treatment and prognosis monitoring. METHODS: Untargeted metabolomics technology was employed to analyze serum metabolic profiles in healthy volunteer controls (NCs) and early stage HCC patients before and after RFA therapy...

Phosphatidic acid (PA) is an anionic lipid that preferentially interacts with proteins in a diverse set of cellular processes such as transport, apoptosis, and neurotransmission. One such interaction is that of the PA lipids with the proteins of voltage-sensitive ion channels. In comparison to several other similarly charged anionic lipids, PA lipids exhibit much stronger interactions. Intrigued and motivated by this finding, we sought out to gain deeper understanding into the electrostatic interactions of anionic lipids with charged proteins...

NME3 is a member of the nucleoside diphosphate kinase (NDPK) family localized on the mitochondrial outer membrane (MOM). Here, we report a role of NME3 in hypoxia-induced mitophagy dependent on its active site phosphohistidine but not the NDPK function. Mice carrying a knock-in mutation in the Nme3 gene disrupting NME3 active site histidine phosphorylation are vulnerable to ischemia/reperfusion-induced infarction and develop abnormalities in cerebellar function. Our mechanistic analysis reveals that hypoxia-induced phosphatidic acid (PA) on mitochondria is essential for mitophagy and the interaction of DRP1 with NME3...

Liposomal carrier systems have emerged as a promising technology for pulmonary drug delivery. This study focuses on two selected liposomal systems, namely, dipalmitoylphosphatidylcholine stabilized by phosphatidic acid and cholesterol (DPPC-PA-Chol) and dipalmitoylphosphatidylcholine stabilized by polyethylene glycol and cholesterol (DPPC-PEG-Chol). First, the research investigates the stability of these liposomal systems during the atomization process using different kinds of nebulizers (air-jet, vibrating mesh, and ultrasonic)...

Lipin-1 is a member of the evolutionarily conserved family of proteins and is expressed predominantly in adipose tissue and skeletal muscle. On the one hand, lipin-1 is an enzyme that catalyzes the dephosphorylation of phosphatidic acid to diacylglycerol (DAG) and thus participates in the metabolic pathways of biosynthesis of storage lipids in the cell, membrane phospholipids, and intracellular signaling molecules. On the other hand, lipin-1 is able to be transported from the cytoplasm to the nucleus and is a coactivator of lipid metabolism gene transcription...

Despite various roles of phosphatidic acid (PA) in cellular functions such as lipid homeostasis and vesicular trafficking, there is a lack of high-affinity tools to study PA in live cells. After analysis of the predicted structure of the LNS2 domain in the lipid transfer protein Nir1, we suspected that this domain could serve as a novel PA biosensor. We created a fluorescently tagged Nir1-LNS2 construct and then performed liposome binding assays as well as pharmacological and genetic manipulations of HEK293A cells to determine how specific lipids affect the interaction of Nir1-LNS2 with membranes...

Mechanosensitive PIEZO2 ion channels play roles in touch, proprioception, and inflammatory pain. Currently, there are no small molecule inhibitors that selectively inhibit PIEZO2 over PIEZO1. The TMEM120A protein was shown to inhibit PIEZO2 while leaving PIEZO1 unaffected. Here we find that TMEM120A expression elevates cellular levels of phosphatidic acid and lysophosphatidic acid (LPA), aligning with its structural resemblance to lipid-modifying enzymes. Intracellular application of phosphatidic acid or LPA inhibited PIEZO2, but not PIEZO1 activity...

Lipins are phosphatidic acid phosphatases (PAP) that catalyze the conversion of phosphatidic acid (PA) to diacylglycerol (DAG). Three lipin isoforms have been identified: lipin-1, -2 and -3. In addition to their PAP activity, lipin-1 and -2 act as transcriptional coactivators and corepressors. Lipins have been intensely studied for their role in regulation of lipid metabolism and adipogenesis; however, lipins are hypothesized to mediate several pathologies, such as those involving metabolic diseases, neuropathy and even cognitive impairment...

The dynamic changes in membrane phospholipids affect membrane biophysical properties and cell signaling, thereby influencing numerous biological processes. Nonspecific phospholipase C (NPC) enzymes hydrolyze common phospholipids to release diacylglycerol (DAG), which is converted to phosphatidic acid (PA) and other lipids. In this study, two Arabidopsis (Arabidopsis thaliana) tandemly arrayed genes, NPC3 and NPC4, were identified as critical factors modulating auxin-controlled plant growth and tropic responses...

PKC-related serine/threonine protein kinase N1 (PKN1) is a protease/lipid-activated protein kinase that acts downstream of the RhoA and Rac1 pathways. PKN1 comprises unique regulatory, hinge region, and PKC homologous catalytic domains. The regulatory domain harbors two homologous regions, i.e., HR1 and C2-like. HR1 consists of three heptad repeats (HR1a, HR1b, and HR1c), with PKN1-(HR1a) hosting an amphipathic high-affinity cardiolipin-binding site for phospholipid interactions. Cardiolipin and C18:1 oleic acid are the most potent lipid activators of PKN1...

OBJECTIVES: To investigate the role and intracellular regulatory mechanisms of double negative T (DNT) cells in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: DNT cells were assessed in murine models, SLE patients and controls using flow cytometry (FCM). DNT cells from either resiquimod (R848) or vehicle-treated C57BL/6 (B6) mice were cultured with B cells from R848-treated mice to explore functions. Differential mTOR pathway signaling in DNT cells measured using FCM and qPCR was validated by rapamycin inhibition...

Trichothecium roseum is a typical necrotrophic fungal pathogen that not only bring about postharvest disease, but contribute to trichothecenes contamination in fruit and vegetables. Phospholipase D (PLD), as an important membrane lipid degrading enzyme, can produce phosphatidic acid (PA) by hydrolyzing phosphatidylcholine (PC) and phosphatidylinositol (PI). PA can promote the production of reactive oxygen species (ROS) by activating the activity of NADPH oxidase (NOX), thereby increasing the pathogenicity to fruit...

BACKGROUND: Soybean is one of the most cultivated crops globally and a staple food for much of the world's population. The annual global crop losses due to infection by Phytophthora sojae is currently estimated at $20B USD, yet we have limited understanding of the role of lipid mediators in the adaptative strategies used by the host plant to limit infection. Since root is the initial site of this infection, we examined the infection process in soybean root infected with Phytophthora sojae using scanning electron microscopy to observe the changes in root morphology and a multi-modal lipidomics approach to investigate how soybean cultivars remodel their lipid mediators to successfully limit infection by Phytophthora sojae...

Two halophilic archaeal strains TS33T and KZCA124 were isolated from two distant salt lakes on the Qinghai-Xizang Plateau, respectively. Culture-independent analysis indicated that these two strains were original inhabitants but low abundant taxa in respective salt lakes. Strains TS33T and KZCA124 were able to grow at 20-60 °C (optimum were 42 and 35 °C, respectively), with 0.9-4.8 M NaCl (optimum were 3.0 and 2.6 M, respectively), with 0-0.7 M MgCl2 (optimum, 0.3 M) and at pH 5...

Rapid conversion of force into a biological signal enables living cells to respond to mechanical forces in their environment. The force is believed to initially affect the plasma membrane and then alter the behavior of membrane proteins. Phospholipase D2 (PLD2) is a mechanosensitive enzyme that is regulated by a structured membrane-lipid site comprised of cholesterol and saturated ganglioside (GM1). Here we show stretch activation of TWIK-related K+ channel (TREK-1) is mechanically evoked by PLD2 and spatial patterning involving ordered GM1 and 4,5-bisphosphate (PIP2 ) clusters in mammalian cells...

Galactolipids comprise the majority of chloroplast membranes in plants, and their biosynthesis requires dephosphorylation of phosphatidic acid at the chloroplast envelope membranes. In Arabidopsis (Arabidopsis thaliana), the lipid phosphate phosphatases LPPγ, LPPε1, and LPPε2 have been previously implicated in chloroplast lipid assembly, with LPPγ being essential, as null mutants were reported to exhibit embryo lethality. Here, we show that lppγ mutants are in fact viable and that LPPγ, LPPε1, and LPPε2 do not appear to have central roles in the plastid pathway of membrane lipid biosynthesis...

A strictly aerobic, Gram-stain-negative, rod-shaped, and motile bacterium, designated strain KMM 296, isolated from the coelomic fluid of the mussel Crenomytilus grayanus , was investigated in detail due to its ability to produce a highly active alkaline phosphatase CmAP of the structural family PhoA. A previous taxonomic study allocated the strain to the species Cobetia marina , a member of the family Halomonadaceae of the class Gammaproteobacteria . However, 16S rRNA gene sequencing showed KMM 296's relatedness to Cobetia amphilecti NRIC 0815T ...

Tumor-associated macrophages (TAMs) are often associated with chemoresistance and resultant poor clinical outcome in solid tumors. Here, we demonstrated that TAMs-released chemokine-C-C motif chemokine 22 (CCL22) in esophageal squamous cell carcinoma (ESCC) stroma was tightly correlated with the chemoresistance of ESCC patients. TAMs-secreted CCL22 was able to block the growth inhibitory and apoptosis-promoting effects of cisplatin on ESCC cells. Mechanistically, CCL22 stimulated intratumoral diacylglycerol kinase α (DGKα) to produce phosphatidic acid (PA), which suppressed the activity of NADPH oxidase 4 (NOX4) and then blocked the overproduction of intratumoral reactive species oxygen (ROS) induced by cisplatin...

Perfluorooctanoic acid (PFOA) is an emerging persistent organic pollutant. Exposure to PFOA was observed to have a correlation with the expression levels of phospholipids. However, there are currently no studies that directly visualize the effects of PFOA on phospholipids. To this end, matrix-assisted laser desorption/ionization time of flight imaging mass spectrometry (MALDI-TOF-IMS) was used to visualize changes in phospholipids in the different tissues of zebrafish following exposure to PFOA. This study found that the major perturbed phospholipids were phosphatidylcholine (PC), diacylglycerol (DG), phosphatidic acid (PA), phosphatidylglycerol (PG), sphingomyelin (SM), and triacylglycerol (TG)...

Parkinson's disease (PD) is a severe pathology that is caused by a progressive degeneration of dopaminergic neurons in substantia nigra pars compacta as well as other areas in the brain. These neurodegeneration processes are linked to the abrupt aggregation of α-synuclein (α-syn), a small protein that is abundant at presynaptic nerve termini, where it regulates cell vesicle trafficking. Due to the direct interactions of α-syn with cell membranes, a substantial amount of work was done over the past decade to understand the role of lipids in α-syn aggregation...