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Theresa Ohlig, Do Viet Le, Andreas Gardemann, Carmen Wolke, Sarah Gürtler, Daniela Peter, Lorenz Schild, Uwe Lendeckel
The mitochondrial phospholipid cardiolipin (CL) has been implicated with mitochondrial morphology, function, and cell proliferation. Changes in CL are often paralleled by changes in the lipid environment of mitochondria that may contribute to mitochondrial function and proliferation. This study aimed to separate the effects of CL content and CL composition from cellular free fatty acid distribution on bioenergetics and proliferation in C6 glioma cells. To this end, cardiolipin synthase and the CL remodelling enzyme, tafazzin, were knocked-down by siRNA in C6 cells...
January 8, 2018: Biochimica et Biophysica Acta
Dariush Mohammadyani, Naveena Yanamala, Alejandro K Samhan Arias, Alexander A Kapralov, German Stepanov, Nick Nuar, Joan Planas-Iglesias, Narinder Sanghera, Valerian E Kagan, Judith Klein-Seetharaman
The interaction between CL and cytochrome c (cyt-c), results in a gain of function of peroxidase activity by cyt-c. Despite intensive research, disagreements on nature and molecular details of this interaction remain. In particular, it is still not known how the interaction triggers the onset of apoptosis. Enzymatic characterization of peroxidase activity has highlighted the need for a critical threshold concentration of CL, a finding of profound physiological relevance in vivo. Using solution NMR, fluorescence spectroscopy, and in silico modeling approaches we here confirm that full binding of cyt-c to the membrane requires a CL:cyt-c threshold ratio of 5:1...
January 6, 2018: Biochimica et Biophysica Acta
Jung-Ah Cho, Tae-Joo Kim, Hye-Jung Moon, Young-Joo Kim, Hye-Kyung Yoon, Seung-Yong Seong
Mitochondrial defects and anti-mitochondrial cardiolipin (CL) antibodies are frequently detected in autoimmune disease patients. CL from dysregulated mitochondria activates various pattern recognition receptors, such as NLRP3. However, the mechanism by which mitochondrial CL activates antigen-presenting cells (APCs) as a damage-associated molecular pattern to prime antigen-specific naïve T cells, which is crucial for T-cell-dependent anti-cardiolipin IgG antibody production in autoimmune diseases is unelucidated...
January 4, 2018: European Journal of Immunology
L Stojanovich, A Djokovic, N Stanisavljevic, M Zdravkovic
Objectives To investigate a possible relationship between cerebrovascular, such as stroke and transient ischaemic attack, and various cutaneous manifestations (livedo reticularis, skin ulcerations, pseudovasculitis lesions, superficial cutaneous necrosis and digital gangrene) in antiphospholipid syndrome (APS). This report is based on a Serbian cohort of APS patients. Methods A total of 508 antiphospholipid syndrome APS patients were assessed: 360 with primary (PAPS) and 148 with APS associated with SLE (SAPS)...
January 1, 2018: Lupus
J Khizroeva, V Bitsadze, A Makatsariya
We have observed the development of a catastrophic antiphospholipid syndrome (CAPS) in a pregnant woman hospitalized at 28 weeks of gestation with a severe preeclampsia. On the same day, an eclampsia attack developed, and an emergency surgical delivery was performed. On the third day, multiorgan failure developed. Examination showed a persistent circulation of lupus anticoagulant, high level of antibodies to cardiolipin, b2-glycoprotein I, and prothrombin. The usual diagnosis of the severe preeclampsia masked a catastrophic antiphospholipid syndrome, exacerbated by the coincident presence of several types of antiphospholipid antibodies...
December 28, 2017: Journal of Maternal-fetal & Neonatal Medicine
Tatyana Romantsov, Karen Gonzalez, Naheda Sahtout, Doreen E Culham, Chelsea Coumoundouros, Jennifer Garner, Craig H Kerr, Limei Chang, Raymond J Turner, Janet M Wood
Osmosensing by transporter ProP is modulated by its cardiolipin (CL)-dependent concentration at the poles of Escherichia coli cells. Other contributors to this phenomenon were sought with the BACterial Two-Hybrid System (BACTH). The BACTH-tagged variants T18-ProP and T25-ProP retained ProP function and localization. Their interaction confirmed the ProP homo-dimerization previously established by protein crosslinking. YdhP, YjbJ and ClsA were prominent among the putative ProP interactors identified by the BACTH system...
December 27, 2017: Molecular Microbiology
Gerburg Keilhoff, Torben Esser, Maximilian Titze, Uwe Ebmeyer, Lorenz Schild
Asphyxial cardiac arrest (ACA)-induced ischemia results in acute and delayed neuronal cell death. The early reperfusion phase is critical for the outcome. Intervention strategies directed to this period are promising to reduce ACA/resuscitation-dependent impairments. This study focused on the evaluation of the protective potential of an extract from Gynostemma pentaphyllum (GP), a plant used in traditional medicine with antioxidative, glucose lowering and neuroprotective activities, in an ACA rat model. We tested the following parameters: i) Basic systemic parameters such as pCO2 and blood glucose value within the first 30 min post-ACA; ii) mitochondrial response by determining activities of citrate synthase, respiratory chain complexes I + III and II + III, and the composition of cardiolipin 6 and 24 h post-ACA; iii) neuronal vitality of the CA1 hippocampal region by immunohistochemistry 24 h and 7 days post-ACA; and iv) cognitive function by a novel object recognition test 7 days post-ACA...
December 2017: Experimental and Therapeutic Medicine
Jenelle Umbsaar, Evan Kerek, Elmar J Prenner
Elevated levels of the essential trace metals cobalt and nickel are associated with a variety of toxic effects, which are not well-understood, and may involve interactions with the lipid membrane. Fluidity changes of biomimetic lipid membranes upon exposure to CoCl2 and NiCl2 were studied using the fluorescent probe Laurdan, which senses changes in environment polarity. Liposomes were prepared by extrusion in 20 mM HEPES + 100 mM NaCl at pH 7.4. Additionally, dynamic light scattering was used to monitor metal induced size changes of liposomes composed of: phosphatidic acid (PA), cardiolipin (CL), phosphatidylglycerol (PG), phosphatidylserine (PS), and phosphatidylcholine (PC), with saturated and unsaturated acyl chains...
December 13, 2017: Chemistry and Physics of Lipids
Kelly M Hines, Adam Waalkes, Kelsi Penewit, Elizabeth A Holmes, Stephen J Salipante, Brian J Werth, Libin Xu
Previous work suggests that altered lipid metabolism may be associated with daptomycin resistance in Gram-positive pathogens, but lipidomic changes underlying resistance are not fully understood. We performed untargeted lipidomics by using three-dimensional hydrophilic interaction liquid chromatography-ion mobility-mass spectrometry (HILIC-IM-MS) to characterize alterations in the lipidomes of daptomycin-susceptible and -resistant isogenic strain pairs of Enterococcus faecalis, Staphylococcus aureus, and Corynebacterium striatum...
November 2017: MSphere
Allison S Dobry, Lauren N Ko, Jessica St John, J Mark Sloan, Sagar Nigwekar, Daniela Kroshinsky
Importance: Calciphylaxis is a rare skin disease with high morbidity and mortality that frequently affects patients with renal disease. Hypercoagulable conditions are frequently observed in both patients with calciphylaxis and those with chronic kidney disease (CKD), complicating our understanding of which hypercoagulable conditions are specific to calciphylaxis. Objective: To identify hypercoagulable conditions that are risk factors for developing calciphylaxis while controlling for CKD...
December 13, 2017: JAMA Dermatology
R R Suleimanova, E A Hudz, D O Melnychuk, L H Kalachniuk
Study of phospholipids changes peculiarities in the liver and dorsal muscles of sterlet (Acipenser ruthenus Linnaeus) may be important to determine the etiology and pathogenesis of fatty liver. We established that the content of total phospholipids in tissues of the liver and dorsal muscles of three-year-old sterlet was less than for two-year-old fish by 15% and 20% (P ≤ 0.01), respectively. The amount of phosphatidylcholine (P ≤ 0.05), phosphatidylethanolamine, phosphatidylserine (P ≤ 0.01), phosphatidylinositol (P ≤ 0...
January 2017: Ukrainian Biochemical Journal
Jyoti Swaroop Kumar, Shubhankar Suman, Sudhir Chandna
Insect cell lines have been utilized as an important higher eukaryotic model system to decipher stress responses and cell death mechanisms. Lepidopteran Sf9 cells (derived from the ovaries of Spodoptera frugiperda) display nearly 100 times higher resistance to ionizing radiation in contrast to mammalian cells, which is partly contributed by an unusually high HDAC activity. However, their response to HDAC inhibition remains to be evaluated. In the present study, the effects of HDAC inhibitor (NaBt) on Sf9 cellular/nuclear morphology, cell cycle progression, DNA damage/repair, redox status, and mitochondrial perturbations were evaluated...
December 13, 2017: Molecular and Cellular Biochemistry
Yakir Guri, Marco Colombi, Eva Dazert, Sravanth K Hindupur, Jason Roszik, Suzette Moes, Paul Jenoe, Markus H Heim, Isabelle Riezman, Howard Riezman, Michael N Hall
Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, leading to steatosis and tumor development. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardiolipin) synthesis...
December 11, 2017: Cancer Cell
Venkatrao Vantaku, Sri Ramya Donepudi, Chandrashekar R Ambati, Feng Jin, Vasanta Putluri, Khoa Nguyen, Kimal Rajapakshe, Cristian Coarfa, Venkata Lokesh Battula, Yair Lotan, Nagireddy Putluri
High-grade Bladder Cancer (BLCA) represents the most aggressive and treatment-resistant cancer that renders the patients with poor survival. However, only a few biomarkers have been identified for the detection and treatment of BLCA. Recent studies show that ganglioside GD2 can be used as cancer biomarker and/or therapeutic target for various cancers. Despite its potential relevance in cancer diagnosis and therapeutics, the role of GD2 is unknown in BLCA. Here, we report for the first time that high-grade BLCA tissues and cell lines have higher expression of GD2 compared to low-grade by high-resolution Mass Spectrometry...
November 10, 2017: Oncotarget
Kentaro Shimasaki, Miho Watanabe-Takahashi, Masato Umeda, Satoru Funamoto, Yoshiro Saito, Noriko Noguchi, Keigo Kumagai, Kentaro Hanada, Fujiko Tsukahara, Yoshiro Maru, Norihito Shibata, Mikihiko Naito, Kiyotaka Nishikawa
Chronic myeloid leukemia (CML) is caused by the chimeric protein p210 BCR-ABL encoded by a gene on the Philadelphia chromosome. Although the kinase domain of p210 BCR-ABL is an active driver of CML, the pathological role of its pleckstrin homology (PH) domain remains unclear. Here, we carried out phospholipid vesicle-binding assays to show that cardiolipin (CL), a characteristic mitochondrial phospholipid, is a unique ligand of the PH domain. Arg726, a basic amino acid in the ligand-binding region, was crucial for ligand recognition...
December 5, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Andrew G Reidenbach, Zachary A Kemmerer, Deniz Aydin, Adam Jochem, Molly T McDevitt, Paul D Hutchins, Jaime L Stark, Jonathan A Stefely, Thiru Reddy, Alex S Hebert, Emily M Wilkerson, Isabel E Johnson, Craig A Bingman, John L Markley, Joshua J Coon, Matteo Dal Peraro, David J Pagliarini
Human COQ8A (ADCK3) and Saccharomyces cerevisiae Coq8p (collectively COQ8) are UbiB family proteins essential for mitochondrial coenzyme Q (CoQ) biosynthesis. However, the biochemical activity of COQ8 and its direct role in CoQ production remain unclear, in part due to lack of known endogenous regulators of COQ8 function and of effective small molecules for probing its activity in vivo. Here, we demonstrate that COQ8 possesses evolutionarily conserved ATPase activity that is activated by binding to membranes containing cardiolipin and by phenolic compounds that resemble CoQ pathway intermediates...
November 24, 2017: Cell Chemical Biology
Non Miyata, Naoto Goda, Keiji Matsuo, Takeshi Hoketsu, Osamu Kuge
Cardiolipin (CL) is synthesized from phosphatidic acid (PA) through a series of enzymatic reactions occurring at the mitochondrial inner membrane (MIM). Ups1-Mdm35 mediates PA transfer from the mitochondrial outer membrane (MOM) to the MIM in the yeast Saccharomyces cerevisiae. Deletion of UPS1 leads to a ~80% decrease in the cellular CL level. However, the CL accumulation in ups1∆ cells is enhanced by the depletion of Ups2, which forms a protein complex with Mdm35 and mediates phosphatidylserine (PS) transfer from the MOM to the MIM for phosphatidylethanolamine (PE) synthesis by a PS decarboxylase, Psd1...
November 27, 2017: Scientific Reports
Akane Maeda, Moe Uchida, Sumire Nishikawa, Tasuku Nishino, Hiroaki Konishi
Cardiolipin and phosphatidic acid-binding protein (CLPABP) controls the stability of the mRNA harboring an AU-rich element (ARE) in the 3' UTR with the help of the RNA stabilizer, human antigen R (HuR). Although CLPABP is localized on the mitochondrial surface as a large protein-RNA complex, its precise role is not yet known. Recently, CLPABP was identified as an N-myristoylated protein. Here, we demonstrate the effects of N-myristoylation on the functions of CLPABP. In the present study, compared to the wild-type protein that possessed the "MG" motif at the N-terminus for N-myristoylation, the mutant CLPABP protein that lacked N-myristoylation modification site was unstable...
November 24, 2017: Biochemical and Biophysical Research Communications
Sardar E Gasanov, Aleksandr A Kim, Lev S Yaguzhinsky, Ruben K Dagda
Cardiolipin (CL) is an anionic phospholipid at the inner mitochondrial membrane (IMM) that facilitates the formation of transient non-bilayer (non-lamellar) structures to maintain mitochondrial integrity. CL modulates mitochondrial functions including ATP synthesis. However, the biophysical mechanisms by which CL generates non-lamellar structures and the extent to which these structures contribute to ATP synthesis remain unknown. We hypothesized that CL and ATP synthase facilitate the formation of non-bilayer structures at the IMM to stimulate ATP synthesis...
November 24, 2017: Biochimica et Biophysica Acta
Clarissa C M Valões, Glaucia V Novak, Juliana B Brunelli, Katia T Kozu, Ricardo K Toma, Clovis A Silva
OBJECTIVE: To assess esophageal involvement (EI) in juvenile localized scleroderma (JLS) population and the possible association between this gastrointestinal manifestation and demographic data, clinical features, laboratory exams, treatments and outcomes. METHODS: For a period of 30 years, 5881 patients with rheumatic diseases were followed in our Pediatric Rheumatology Division. EI was defined by the presence of symptoms (solid/liquid dysphagia, heartburn, esophageal regurgitation, nausea/vomiting and epigastralgia) and confirmed by at least one EI exam abnormality: barium contrast radiography, upper gastrointestinal endoscopy and 24-hour esophageal pH-monitoring...
November 2017: Revista Brasileira de Reumatologia
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