Theophylline treatment improves mitochondrial function after upper cervical spinal cord hemisection. 2010

Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA.

The importance of mitochondria in spinal cord injury has mainly been attributed to their participation in apoptosis at the site of injury. But another aspect of mitochondrial function is the generation of more than 90% of cellular energy in the form of ATP, mediated by the oxidative phosphorylation (OxPhos) process. Cytochrome c oxidase (CcO) is a central OxPhos component and changes in its activity reflect changes in energy demand. A recent study suggests that respiratory muscle function in chronic obstructive pulmonary disease (COPD) patients is compromised via alterations in mitochondrial function. In an animal model of cervical spinal cord hemisection (C2HS) respiratory dysfunction, we have shown that theophylline improves respiratory function. In the present study, we tested the hypothesis that theophylline improves respiratory function at the cellular level via improved mitochondrial function in the C2HS model. We demonstrate that CcO activity was significantly (33%) increased in the spinal cord adjacent to the site of injury (C3-C5), and that administration of theophylline (20mg/kg 3x daily orally) after C2HS leads to an even more pronounced increase in CcO activity of 62% compared to sham-operated animals. These results are paralleled by a significant increase in cellular ATP levels (51% in the hemidiaphragm ipsilateral to the hemisection). We conclude that C2HS increases energy demand and activates mitochondrial respiration, and that theophylline treatment improves energy levels through activation of the mitochondrial OxPhos process to provide energy for tissue repair and functional recovery after paralysis in the C2HS model.

UI MeSH Term Description Entries
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
D010085 Oxidative Phosphorylation Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. Phosphorylation, Oxidative,Oxidative Phosphorylations,Phosphorylations, Oxidative
D010726 Phosphodiesterase Inhibitors Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases. Phosphodiesterase Antagonists,Phosphodiesterase Inhibitor,Phosphoric Diester Hydrolase Inhibitors,Antiphosphodiesterases,Inhibitor, Phosphodiesterase
D002574 Cervical Vertebrae The first seven VERTEBRAE of the SPINAL COLUMN, which correspond to the VERTEBRAE of the NECK. Cervical Spine,Cervical Spines,Spine, Cervical,Vertebrae, Cervical
D003576 Electron Transport Complex IV A multisubunit enzyme complex containing CYTOCHROME A GROUP; CYTOCHROME A3; two copper atoms; and 13 different protein subunits. It is the terminal oxidase complex of the RESPIRATORY CHAIN and collects electrons that are transferred from the reduced CYTOCHROME C GROUP and donates them to molecular OXYGEN, which is then reduced to water. The redox reaction is simultaneously coupled to the transport of PROTONS across the inner mitochondrial membrane. Cytochrome Oxidase,Cytochrome aa3,Cytochrome-c Oxidase,Cytochrome Oxidase Subunit III,Cytochrome a,a3,Cytochrome c Oxidase Subunit VIa,Cytochrome-c Oxidase (Complex IV),Cytochrome-c Oxidase Subunit III,Cytochrome-c Oxidase Subunit IV,Ferrocytochrome c Oxygen Oxidoreductase,Heme aa3 Cytochrome Oxidase,Pre-CTOX p25,Signal Peptide p25-Subunit IV Cytochrome Oxidase,Subunit III, Cytochrome Oxidase,p25 Presequence Peptide-Cytochrome Oxidase,Cytochrome c Oxidase,Cytochrome c Oxidase Subunit III,Cytochrome c Oxidase Subunit IV,Oxidase, Cytochrome,Oxidase, Cytochrome-c,Signal Peptide p25 Subunit IV Cytochrome Oxidase,p25 Presequence Peptide Cytochrome Oxidase
D003964 Diaphragm The musculofibrous partition that separates the THORACIC CAVITY from the ABDOMINAL CAVITY. Contraction of the diaphragm increases the volume of the thoracic cavity aiding INHALATION. Respiratory Diaphragm,Diaphragm, Respiratory,Diaphragms,Diaphragms, Respiratory,Respiratory Diaphragms
D004576 Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Electromyogram,Surface Electromyography,Electromyograms,Electromyographies,Electromyographies, Surface,Electromyography, Surface,Surface Electromyographies
D004734 Energy Metabolism The chemical reactions involved in the production and utilization of various forms of energy in cells. Bioenergetics,Energy Expenditure,Bioenergetic,Energy Expenditures,Energy Metabolisms,Expenditure, Energy,Expenditures, Energy,Metabolism, Energy,Metabolisms, Energy
D005260 Female Females
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2

Related Publications

Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
July 1996, Experimental neurology,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
March 1958, Biulleten' eksperimental'noi biologii i meditsiny,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
August 2002, Journal of neurotrauma,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
November 2014, Experimental neurology,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
February 2014, Respiratory physiology & neurobiology,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
November 2002, Brain research,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
December 2022, Brain : a journal of neurology,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
January 2017, Behavioural neurology,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
January 2006, The journal of spinal cord medicine,
Maik Hüttemann, and Kwaku D Nantwi, and Icksoo Lee, and Jenney Liu, and Syed Mohiuddin, and Theodor Petrov
October 2000, Journal of applied physiology (Bethesda, Md. : 1985),
Copied contents to your clipboard!