Differential upregulation of heme oxygenase-1 (HSP32) in glial cells after oxidative stress and in demyelinating disorders. 2007

Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
Department of Biology, Molecular Neurobiology, University of Oldenburg, D-26111 Oldenburg, Germany.

Oxidative stress is implicated in the pathogenesis of demyelinating disorders and inflammatory responses. Heme oxygenase-1 (HO-1; HSP32) is a small heat shock protein (HSP) with enzymatic activity, which is inducible by oxidative stress. In this study we analyzed autopsy and biopsy brain samples of patients with multiple sclerosis (MS) and ADEM (acute disseminated leucoencephalomyelits) and spinal cord lesions of mouse EAE (experimental autoimmune encephalomyelitis), which was actively induced by immunization with myelin oligodendrocyte glycoprotein (MOG35-55) peptide, for the presence of HO-1. HO-1 was observed in glial cells during different stages: (1) during acute phases of mainly inflammatory diseases (EAE and ADEM) expression of HO-1 was prominent in microglia/macrophages and astrocytes, and upregulation correlated with inflammation, and (2) in early MS lesions HO-1 was expressed in oligodendrocytes. Furthermore, in glial cell cultures, we can show that upregulation of HO-1 in oligodendrocytes was paralleled by severe morphological damage. Oligodendrocytes underwent apoptotic cell death at a concentration of hydrogen peroxide (50-200 microM) which did not affect astrocytes or microglia. Using oligodendroglial OLN-93 cells, we demonstrate that oxidative stress led to mitochondrial impairment and the disorganization of the microtubule network. Zinc protoporphyrin, an inhibitor of HO-1, augmented the cytotoxic consequences of hydrogen peroxide in OLN-93 cells. Hence, the presence of HO-1 in EAE, ADEM, and MS points to the involvement of oxidative stress and a role of HO-1 in the pathogenesis of the diseases. The data suggest that stress-induced HO-1 initially plays a protective role, while its chronic upregulation, might contribute to oligodendroglial cell death rather than providing protection.

UI MeSH Term Description Entries
D008264 Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.) Bone Marrow-Derived Macrophages,Monocyte-Derived Macrophages,Macrophage,Macrophages, Monocyte-Derived,Bone Marrow Derived Macrophages,Bone Marrow-Derived Macrophage,Macrophage, Bone Marrow-Derived,Macrophage, Monocyte-Derived,Macrophages, Bone Marrow-Derived,Macrophages, Monocyte Derived,Monocyte Derived Macrophages,Monocyte-Derived Macrophage
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D009836 Oligodendroglia A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system. Interfascicular Oligodendroglia,Oligodendrocytes,Perineuronal Oligodendroglia,Perineuronal Satellite Oligodendroglia Cells,Perivascular Oligodendroglia,Satellite Cells, Perineuronal, Oligodendroglia,Perineuronal Satellite Oligodendrocytes,Interfascicular Oligodendroglias,Oligodendrocyte,Oligodendrocyte, Perineuronal Satellite,Oligodendrocytes, Perineuronal Satellite,Oligodendroglia, Interfascicular,Oligodendroglia, Perineuronal,Oligodendroglia, Perivascular,Perineuronal Satellite Oligodendrocyte,Satellite Oligodendrocyte, Perineuronal,Satellite Oligodendrocytes, Perineuronal
D011524 Protoporphyrins Porphyrins with four methyl, two vinyl, and two propionic acid side chains attached to the pyrrole rings. Protoporphyrin IX occurs in hemoglobin, myoglobin, and most of the cytochromes.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003711 Demyelinating Diseases Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system. Clinically Isolated CNS Demyelinating Syndrome,Clinically Isolated Syndrome, CNS Demyelinating,Demyelinating Disorders,Demyelination,Demyelinating Disease,Demyelinating Disorder,Demyelinations
D004681 Encephalomyelitis, Autoimmune, Experimental An experimental animal model for central nervous system demyelinating disease. Inoculation with a white matter emulsion combined with FREUND'S ADJUVANT, myelin basic protein, or purified central myelin triggers a T cell-mediated immune response directed towards central myelin. The pathologic features are similar to MULTIPLE SCLEROSIS, including perivascular and periventricular foci of inflammation and demyelination. Subpial demyelination underlying meningeal infiltrations also occurs, which is also a feature of ENCEPHALOMYELITIS, ACUTE DISSEMINATED. Passive immunization with T-cells from an afflicted animal to a normal animal also induces this condition. (From Immunol Res 1998;17(1-2):217-27; Raine CS, Textbook of Neuropathology, 2nd ed, p604-5) Autoimmune Encephalomyelitis, Experimental,Encephalomyelitis, Allergic,Encephalomyelitis, Experimental Autoimmune,Allergic Encephalomyelitis,Allergic Encephalomyelitis, Experimental,Autoimmune Experimental Encephalomyelitis,Experimental Allergic Encephalomyelitis,Experimental Autoimmune Encephalomyelitis,Encephalomyelitis, Autoimmune Experimental,Encephalomyelitis, Experimental Allergic,Experimental Allergic Encephalomyelitides,Experimental Encephalomyelitis, Autoimmune
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D005260 Female Females

Related Publications

Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
August 2009, Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics,
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
May 2011, Translational research : the journal of laboratory and clinical medicine,
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
August 2016, Experimental biology and medicine (Maywood, N.J.),
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
April 2010, Journal of neurochemistry,
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
November 2005, Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi,
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
April 2023, Cancer medicine,
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
January 2012, International journal of hypertension,
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
August 2013, American journal of physiology. Renal physiology,
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
January 2016, Oxidative medicine and cellular longevity,
Thomas Stahnke, and Christine Stadelmann, and Anne Netzler, and Wolfgang Brück, and Christiane Richter-Landsberg
January 1997, The American journal of physiology,
Copied contents to your clipboard!