LPS changes energy metabolism in microglial N9 and cholinergic SN56 neuronal cells

• Autorzy: Klimaszrwska-Lata J. , Gul-Hinc S. , Bielarczyk H. , Ronowska A. , Bizon-Zygmanska D. , Dys A. , Szutowicz A.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Inhibition of brain energy metabolism, accompanied by inflammatory activation of microglial cells is a characteristic feature of several neurodegenerative brain diseases, including Alzheimer’s, aluminum or vascular encephalopathies. Microglial inflammatory response to neurotoxic signals may contribute to neuronal degeneration through excessive production of nitric oxide (NO) and a vast range of pro-inflammatory cytokines. The aim of this work was to investigate whether and how lipopolysaccharide (LPS), and its key mediator NO, may differentially affect energy and acetyl-CoA metabolism of microglial N9 and cholinergic SN56 neuroblastoma cells. METHODS: In experimential model cell cultures were used: N9 murine microglial cells and SN56.B5.G4 cholinergic murine neuroblastoma cells. RESULTS: Exposition of murine microglial N9 cells to LPS caused concentration-dependent several-fold increases of nitrogen oxide synthesis, accompanied by inhibition of pyruvate dehydrogenase complex (PDHC), aconitase and α-ketoglutarate dehydrogenase complex (KDHC) activities, and by depletion of acetyl-CoA, but by small losses in ATP content and cell viability. On the other hands, SN56 cells were insensitivity to LPS, which was probably caused by lower than in N9, expression of TLR4. However, exogenous NO caused inhibition of PDHC and aconitase activities, depletion of acetyl-CoA and loss of SN56 cells viability. Microglial cells appeared to be more resistant than neuronal cells to acetyl-CoA and ATP depletion evoked by these neurodegenerative condition. CONCLUSIONS: These data indicate that preferential susceptibility of cholinergic neurons to neurodegenerative insults may results from competition for acetyl-CoA between mitochondrial energyproducing and cytoplasmic acetylocholine synthesizing pathways. One of the reasons for greater resistance of microglial cells to cytotoxic inputs could be their lower energy demand. Supported by MNSW project MN 01-0067/08 and GUMed fund ST-57.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S70

Twórcy

autor

Klimaszrwska-Lata J.

• Chair of Clinical Biochemistry, Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Gul-Hinc S.

• Chair of Clinical Biochemistry, Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Bielarczyk H.

• Chair of Clinical Biochemistry, Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Ronowska A.

• Chair of Clinical Biochemistry, Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Bizon-Zygmanska D.

• Chair of Clinical Biochemistry, Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Dys A.

• Chair of Clinical Biochemistry, Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland

autor

Szutowicz A.

• Chair of Clinical Biochemistry, Department of Laboratory Medicine, Medical University of Gdansk, Gdansk, Poland