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Hwei-Ming Peng, Chase Barlow, Richard J Auchus
Unlike most of the drug-metabolizing cytochrome P450s, microsomal P450 17A1 and mitochondrial P450 11B2 catalyze sequential multi-step reactions in steroid biosynthesis. The membrane phospholipid composition might be one parameter that modulates the efficiency and processivity of specific pathways. Here we systematically examined the effects of physiologically relevant phospholipids on the catalysis of purified P450 17A1, P450 11B2, and P450 11B1 in reconstituted assay systems. Both dioleoylphosphatidylcholine (DOPC, 18:1) and dilauroylphosphatidylcholine (DLPC, 12:0) were found to be very efficient in reconstituting 17-hydroxylase and 17,20-lyase reactions of P450 17A1...
March 13, 2018: Journal of Steroid Biochemistry and Molecular Biology
Amaris Castanon, Grant Pierre, Rohan Willis, E Nigel Harris, Elizabeth Papalardo, Zurina Romay-Penabad, Alvaro Schleh, Praveen Jajoria, Monica Smikle, Karel DeCeulaer, Anne Tebo, Troy Jaskowski, Marta M Guerra, D Ware Branch, Jane E Salmon, Michelle Petri, Emilio B Gonzalez
Objectives: We evaluate the performance characteristics of antiphosphatidylserine (anti-PS), antiphosphatidylinositol (anti-PI), and antiphospholipid mixture (APhL) enzyme-linked immunosorbent assays (ELISAs) compared with anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) in a large group of patients with antiphospholipid (aPL)-related diseases. Methods: Serum samples from 548 patients from the Hopkins and Jamaican systemic lupus erythematosus cohorts, the PROMISSE cohort, and the Antiphospholipid Standardization Laboratory were examined for immunoglobulin G (IgG)/immunoglobulin M (IgM) positivity in aCL, anti-β2GPI, anti-PS, anti-PI, and APhL ELISA assays...
March 14, 2018: American Journal of Clinical Pathology
Hao Zhou, Pingjun Zhu, Jin Wang, Hong Zhu, Jun Ren, Yundai Chen
Disturbed mitochondrial homeostasis contributes to the pathogenesis of cardiac ischemia reperfusion (IR) injury, although the underlying mechanism remains elusive. Here, we demonstrated that casein kinase 2α (CK2α) was upregulated following acute cardiac IR injury. Increased CK2α was shown to be instrumental to mitochondrial damage, cardiomyocyte death, infarction area expansion and cardiac dysfunction, whereas cardiac-specific CK2α knockout (CK2αCKO ) mice were protected against IR injury and mitochondrial damage...
March 14, 2018: Cell Death and Differentiation
Wataru Sato, Takeshi Uchida, Tomohide Saio, Koichiro Ishimori
Cytochrome c (Cyt c) was rapidly oxidized by molecular oxygen in the presence, but not absence of PEG. The redox potential of heme c was determined by the potentiometric titration to be +236 ± 3 mV in the absence of PEG, which was negatively shifted to +200 ± 4 mV in the presence of PEG. The underlying the rapid oxidation was explored by examining the structural changes in Cyt c in the presence of PEG using UV-visible absorption, circular dichroism, resonance Raman, and fluorescence spectroscopies...
March 11, 2018: Biochimica et Biophysica Acta
Ayako Ohyama, Hiroto Tsuboi, Hisashi Noma, Mayu Terasaki, Masaru Shimizu, Hirofumi Toko, Fumika Honda, Mizuki Yagishita, Hiroyuki Takahashi, Hiromitsu Asashima, Shinya Hagiwara, Yuya Kondo, Isao Matsumoto, Takayuki Sumida
OBJECTIVES: The purpose of this study is to clarify associations between maternal clinical features and adverse pregnancy outcomes (APOs) in mothers with connective tissue diseases (CTDs). METHODS: We retrospectively examined maternal clinical features including backgrounds, autoantibodies, CTD flare-ups, and therapies during pregnancies as well as fetal outcomes in 90 pregnancies (66 mothers) at our hospital from January 2006 to September 2016. RESULTS: Underlying CTDs were SLE (N = 41), MCTD (N = 10), RA (N = 15), SS (N = 10), and others (N = 14)...
March 13, 2018: Modern Rheumatology
Sei Kuriyama, Tadahiro Tsuji, Tetsushi Sakuma, Takashi Yamamoto, Masamistu Tanaka
The anti-apoptotic nature of cancer cells often impedes the effects of anti-cancer therapeutic agents. Multiple death signals influence mitochondria during apoptosis, and though many studies have attempted to elucidate these complicated pathways, Bax oligomerization, an important step in the process, remains controversial. Here we demonstrate that pleckstrin-homology N1 (PLEKHN1), also known as cardiolipin phosphatidic acid binding protein, plays pro-apoptotic roles during reactive oxygen species (ROS)-induced apoptosis...
December 2018: Cell Death Discovery
Christopher M Jenkins, Kui Yang, Gaoyuan Liu, Sung Ho Moon, Beverly G Dilthey, Richard W Gross
Plasmalogens are phospholipids critical for cell function and signaling that contain a vinyl-ether linkage at the   sn -1 position and are highly enriched in arachidonic acid (AA) at the sn -2 position. However, the enzyme(s) responsible for the cleavage of the vinyl ether linkage in plasmalogens has remained elusive.  Herein, we report that cytochrome c , in the presence of either cardiolipin (CL), O2 and H2 O2 , or oxidized CL and O2 , catalyzes the oxidation of the plasmalogen vinyl ether linkage, promoting its hydrolytic cleavage and resultant production of 2-AA-lysolipids and highly reactive α-hydroxy fatty aldehydes...
March 12, 2018: Journal of Biological Chemistry
Shay Schneider, Joseph Kapelushnik, Mordechai Kraus, Sabri El Saied, Itai Levi, Daniel Michael Kaplan
PURPOSE: Otogenic lateral sinus thrombosis (OLST) is an intracranial, potentially life-threatening complication of acute and chronic otitis media. Since congenital thrombophilic disorders are risk factors for cerebral venous thrombosis, OLST may be related to thrombophilia. The aim of our study was twofold: to evaluate whether patients who suffered from OLST in childhood also have thrombophilia, and whether these patients experienced thromboembolic episodes in future years. STUDY DESIGN: Retrospective case series...
March 7, 2018: American Journal of Otolaryngology
Mehmet Tecellioglu, Ozden Kamisli, Suat Kamisli, Fatma Ebru Yucel, Cemal Ozcan
BACKGROUND: Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. AIMS: To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. METHODS: Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified...
March 9, 2018: Irish Journal of Medical Science
A R Ramirez, O L Acosta, M B Maya, M El-Hafidi
In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment...
March 7, 2018: Current Molecular Medicine
Bharat Kumar, Jennifer Strouse, Melissa Swee, Petar Lenert, Manish Suneja
INTRODUCTION: Hydralazine is an antihypertensive medication that has been associated with drug-induced lupus erythematosus (DIL) as well as ANCA-associated vasculitis (AAV). Although rare, early diagnosis is critical since drug cessation is the mainstay of therapy. This retrospective study aims to characterize the clinical, laboratory, and histopathologic features of this disease. METHODS: Once approval was obtained from the Institutional Review Board at the University of Iowa, all patients carrying a diagnosis of vasculitis (ICD9 code: 447...
January 12, 2018: Seminars in Arthritis and Rheumatism
Kwang Sik Suh, Eun Mi Choi, Hyun-Sook Kim, So Young Park, Sang Ouk Chin, Sang Youl Rhee, Youngmi Kim Pak, Wonchae Choe, Joohun Ha, Suk Chon
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The aim of the current study was to explore the role of xanthohumol in modulating the toxicity of TCDD in MC3T3-E1 osteoblastic cells. In cells treated with TCDD alone, intracellular Ca2+ concentrations, mitochondrial membrane potential disruption, reactive oxygen species production, cardiolipin peroxidation, nitric oxide release and cytochrome P450 1A1 expression were significantly increased...
March 8, 2018: Journal of Applied Toxicology: JAT
Ari Dwi Nugraheni, Chunguang Ren, Yorifumi Matsumoto, Satoshi Nagao, Masaru Yamanaka, Shun Hirota
The Met80-heme iron bond of cytochrome c (cyt c) is cleaved by the interaction of cyt c with cardiolipin (CL) in membranes. The Met80 dissociation enhances the peroxidase activity of cyt c and triggers cyt c release from mitochondrion to the cytosol at the early stage of apoptosis. This paper demonstrates the selective oxidation of Met80 for the reaction of ferric cyt c with a peroxide, meta-chloroperbenzoic acid (mCPBA), in the presence of CL-containing liposomes by formation of a ferryl species (Compound I)...
February 24, 2018: Journal of Inorganic Biochemistry
John W Patrick, Christopher D Boone, Wen Liu, Gloria M Conover, Yang Liu, Xiao Cong, Arthur Laganowsky
Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein-lipid assemblies. Despite this inherent complexity, the identification of specific protein-lipid interactions and the crucial role of lipids in the folding, structure, and function of membrane proteins is emerging from an increasing number of reports. Fundamental questions remain, however, regarding the ability of specific lipid binding events to membrane proteins to alter remote binding sites for lipids of a different type, a property referred to as allostery [Monod J, Wyman J, Changeux JP (1965) J Mol Biol 12:88-118]...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alex-Rose Pogmore, Kenneth H Seistrup, Henrik Strahl
Rather than being homogenous diffusion-dominated structures, biological membranes can exhibit areas with distinct composition and characteristics, commonly termed as lipid domains. Arguably the most comprehensively studied examples in bacteria are domains formed by cardiolipin, which have been functionally linked to protein targeting, the cell division process and the mode of action of membrane-targeting antimicrobials. Cardiolipin domains were originally identified in the Gram-negative model organism Escherichia coli based on preferential staining by the fluorescent membrane dye nonylacridine orange (NAO), and later reported to also exist in other Gram-negative and -positive bacteria...
March 5, 2018: Microbiology
Noel-Marie Plonski, Bianca Bissoni, Madara Hetti Arachchilage, Karl Romstedt, Edgar E Kooijman, Helen Piontkivska
Unicellular flagellates that make up the class Kinetoplastida include multiple parasites responsible for public health concerns, including Trypanosoma brucei and T. cruzi (agents of African sleeping sickness and Chagas disease, respectively), and various Leishmania species, which cause leishmaniasis. These diseases are generally difficult to eradicate, with treatments often having lethal side effects and/or being effective only during the acute phase of the diseases, when most patients are still asymptomatic...
February 28, 2018: Gene
Amel Karaa, Richard Haas, Amy Goldstein, Jerry Vockley, W Douglas Weaver, Bruce H Cohen
OBJECTIVE: To assess the safety and efficacy of elamipretide, an aromatic-cationic tetrapeptide that readily penetrates cell membranes and transiently localizes to the inner mitochondrial membrane where it associates with cardiolipin, in adults with primary mitochondrial myopathy (PMM). METHODS: A Study Investigating the Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy (MMPOWER) was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial of elamipretide in 36 participants with genetically confirmed PMM...
March 2, 2018: Neurology
Gilles Fouret, Sylvie Gaillet, Jerome Lecomte, Beatrice Bonafos, Ferdinand Djohan, Bruno Barea, Eric Badia, Charles Coudray, Christine Feillet-Coudray
The incidence of obesity and its metabolic complications are rapidly increasing and become a major public health issue. This trend is associated with an increase in the prevalence of non-alcoholic fatty liver disease (NAFLD), insulin resistance and diabetes. The sequence of events leading to NAFLD progression and mitochondrial dysfunction and their interrelation remains to be elucidated. This study aimed to explore the installation and progression of NAFLD and its association with the liver mitochondrial structure and activity changes in rats fed an obesogenic diet up to 20 weeks...
February 2018: British Journal of Nutrition
Yu-Jen Chao, Wen-Hsin Wu, Maria Balazova, Ting-Yuan Wu, Jamie Lin, Yi-Wen Liu, Yuan-Hao Howard Hsu
The zebrafish (Danio rerio) is an important and widely used vertebrate model organism for the study of human diseases which include disorders caused by dysfunctional mitochondria. Mitochondria play an essential role in both energy metabolism and apoptosis, which are mediated through a mitochondrial phospholipid cardiolipin (CL). In order to examine the cardiolipin profile in the zebrafish model, we developed a CL analysis platform by using liquid chromatography-mass spectrometry (LC-MS). Meanwhile, we tested whether chlorella diet would alter the CL profile in the larval fish, and in various organs of the adult fish...
2018: PloS One
Lara Console, Mariafrancesca Scalise, Annamaria Tonazzi, Nicola Giangregorio, Cesare Indiveri
Exosomes are extracellular vesicles involved in cell-to-cell communication. Previous large scale proteomics revealed that they contain SLC proteins. However, no data on the function of exosomal SLCs is available, so far. An SLC localized in exosomes was here characterized for the first time: the carnitine transporter OCTN2 (SLC22A5). The protein was detected by Western Blot analysis in HEK293 exosomes. To investigate the functional properties of the exosomal OCTN2, the proteins extracted from vesicles were reconstituted into proteolipsomes and the transport function was measured as uptake of3 H-carnitine...
February 28, 2018: Scientific Reports
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