Reprod. Nutr. Dev. 45 (2005) 633-646
DOI: 10.1051/rnd:2005050

Regulation of intracellular calcium levels by polyunsaturated fatty acids, arachidonic acid and docosahexaenoic acid, in astrocytes: possible involvement of phospholipase A₂

Marina Sergeeva^{a, b}, Mikhail Strokin^a and Georg Reiser<sup>a

a</sup>  Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Institut für Neurobiochemie, Leipziger Strasse 44, 39120 Magdeburg, Germany
^b  Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia

(Received 28 February 2005; accepted 9 May 2005)

Abstract - Pathological conditions in the brain, such as ischemia, trauma and seizure are accompanied by increased levels of free n-6 and n-3 polyunsaturated fatty acids (PUFA), mainly arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3). A neuroprotective role has been suggested for PUFA. For investigation of the potential molecular mechanisms involved in neuroprotection by PUFA, we studied the regulation of the concentration of intracellular Ca²⁺ ([Ca²⁺]_i) in rat brain astrocytes. We evaluated the presence of extracellular PUFA and the release of intracellular PUFA. Interestingly, only the constitutive brain PUFA AA and DHA, but not eicosapentaenoic acid (EPA) had prominent effects on intracellular Ca²⁺. AA and DHA suppressed [Ca²⁺]_i oscillation, inhibited store-operated Ca²⁺ entry, and reduced the amplitudes of Ca²⁺ responses evoked by agonists of G protein-coupled receptors. Moreover, prolonged exposure of astrocytes to AA and DHA brought the cells to a new steady state of a moderately elevated [Ca²⁺]_i level, where the cells became virtually insensitive to external stimuli. This new steady state can be considered as a mechanism of self-protection. It isolates disturbed parts of the brain, because AA and DHA reduce pathological overstimulation in the tissue surrounding the damaged area. In inflammation-related events, frequently AA and DHA exhibit opposite effects. However, in astrocytes AA and DHA exerted comparable effects on [Ca²⁺]_i. Extracellularly added AA and DHA, but not EPA, were also able to induce the release of [³H]AA from prelabeled astrocytes. Therefore, we also suggest the involvement of phospholipase A₂ activation and lysophospholipid generation in the regulation of intracellular Ca²⁺ in astrocytes.

Key words: arachidonic acid / docosahexaenoic acid / eicosapentaenoic acid / prostglandins / cycloxygenase / CNS / essential fatty acid / neuroprotection

Corresponding author: Georg Reiser Georg.Reiser@Medizin.Uni-Magdeburg.de

© INRA, EDP Sciences 2005