Relationships between acetyl-CoA level and function of fenotypically modified N9 murine microglial cells

• Autorzy: Klimaszewska-Lata J. , Ronowska A. , Bielarczyk H. , Szutowicz A.
• Języki publikacji: EN

Abstrakty

EN

Neurodegenerative lesions in cholinergic encephalopathies include an excessive activation of microglia, which may aggravate this process. Infl amatory cytokines were reported to affect viability of cultured cholinergic cells, through the infl uence on their acetyl-CoA metabolism. The aim of this work was to investigate whether phenotypic modifi cations of N9 microglia by common neuron-differentiating stimuli can alter its energy metabolism, viability and biological activity in neurodegenerative conditions. In basal conditions lipopolysaccharide (LPS) slightly decreased PDH activity and acetyl-CoA content and activated NO synthesis (600%). The cyclic AMP alone (0.25 mM), caused 15% increase of nonviable cells at 300% rise in NO synthesis and 50 and 30% decreases in acetyl-CoA and ATP contents, respectively. In such conditions LPS resulted in further increase of NO accumulation and aggravated loss of cell viability and their acetyl-CoA content. In basic conditions retinoic acid (RA) alone did not alter viability and NO synthesizing capacity but increased acetyl-CoA and blunted cytotoxic potencies of cAMP and LPS to N9. RA-evoked restoration of N9 cell viability was accompanied by the increase in their acetyl-CoA content. These data indicate that activation of microglia depletes their acetyl-CoA, making them more vulnerable to cytotoxic insults. On the contrary, rescue of microglia by RA-signaling pathways is connected with restoration their acetylCoA pool. Supported by MNiSW projects P05A 11030 and NN401 2333 33 and AMG fund St-57.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.94

Twórcy

autor

Klimaszewska-Lata J.

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

autor

Ronowska A.

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

autor

Bielarczyk H.

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

autor

Szutowicz A.

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