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SHR Neuro Krebs Kardio Lipid

Nusshold, C; Kollroser, M; Köfeler, H; Rechberger, G; Reicher, H; Ullen, A; Bernhart, E; Waltl, S; Kratzer, I; Hermetter, A; Hackl, H; Trajanoski, Z; Hrzenjak, A; Malle, E; Sattler, W.
Hypochlorite modification of sphingomyelin generates chlorinated lipid species that induce apoptosis and proteome alterations in dopaminergic PC12 neurons in vitro.
Free Radic Biol Med. 2010; 48(12): 1588-1600. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Bernhart Eva Maria
Hrzenjak Andelko
Köfeler Harald
Kollroser Manfred
Kratzer Ingrid
Malle Ernst
Nusshold Christoph
Reicher Helga
Sattler Wolfgang
Üllen Andreas
Waltl Sabine Evelyn
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Number of Figures: 8
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Abstract:
Recent observations link myeloperoxidase (MPO) activation to neurodegeneration. In multiple sclerosis MPO is present in areas of active demyelination where the potent oxidant hypochlorous acid (HOCl), formed by MPO from H(2)O(2) and chloride ions, could oxidatively damage myelin-associated lipids. The purpose of this study was (i) to characterize reaction products of sphingomyelin (SM) formed in response to modification by HOCl, (ii) to define the impact of exogenously added SM and HOCl-modified SM (HOCl-SM) on viability parameters of a neuronal cell line (PC12), and (iii) to study alterations in the PC12 cell proteome in response to SM and HOCl-SM. MALDI-TOF-MS analyses revealed that HOCl, added as reagent or generated enzymatically, transforms SM into chlorinated species. On the cellular level HOCl-SM but not SM induced the formation of reactive oxygen species. HOCl-SM induced severely impaired cell viability, dissipation of the mitochondrial membrane potential, and activation of caspase-3 and DNA damage. Proteome analyses identified differential expression of specific subsets of proteins in response to SM and HOCl-SM. Our results demonstrate that HOCl modification of SM results in the generation of chlorinated lipid species with potent neurotoxic properties. Given the emerging connections between the MPO-H(2)O(2)-chloride axis and neurodegeneration, this chlorinating pathway might be implicated in neuropathogenesis.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Apoptosis - drug effects
Blotting, Western -
Brain Chemistry -
Cell Line -
Dopamine - metabolism
Electrophoresis, Gel, Two-Dimensional -
Fourier Analysis -
Halogenation -
Hypochlorous Acid - pharmacology
Image Processing, Computer-Assisted -
Lipids - chemistry
Membrane Potential, Mitochondrial -
Mice -
Mice, Inbred C57BL -
Neurons - metabolism
Oxidants - pharmacology
Oxidative Stress - physiology
Proteome - chemistry
Rats -
Reactive Oxygen Species - metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization -
Sphingomyelins - chemistry

Find related publications in this database (Keywords)
Chlorinative stress
Chlorohydrins
2D-DIGE
Glycolysis
Lipotoxicity
Proteomics
MPO-H2O2-chloride system
Free radicals
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