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

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,. 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 Ca 2+ ([Ca 2+ ] 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 Ca 2+ . AA and DHA suppressed [Ca 2+ ] i oscillation, inhibited store-operated Ca 2+ entry, and reduced the amplitudes of Ca 2+ 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 [Ca 2+ ] 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 [Ca 2+ ] i . Extracellularly added AA and DHA, but not EPA, were also able to induce the release of [ 3 H]AA from prelabeled astrocytes. Therefore, we also suggest the involvement of phospholipase A 2 activation and lysophospholipid generation in the regulation of intracellular Ca 2+ in astrocytes.

Calcium Dysregulation and Homeostasis of Neural Calcium in the Molecular Mechanisms of Neurodegenerative Diseases Provide Multiple Targets for Neuroprotection

“…For example, the protease thrombin at low concentrations mediates hippocampal neuroprotection against ischemia via activation of protease-activated receptors, but thrombin causes neuronal degeneration at high concentrations (95). Further, the involvement of phospholipase A 2 activation in the up-or downregulation of [Ca 2þ ] i in astrocytes promises neuroprotection (88). The development of better-focused antiexcitotoxic strategies requires considerations of pro-survival NMDAR signaling.…”

Effect of Docosahexaenoic Acid on Voltage-Independent Ca²⁺ Entry Pathways in Cultured Vascular Smooth Muscle Cells Stimulated with 5-Hydroxytryptamine

“…In astrocytes, it has been reported that acute DHA treatment inhibits SOCE. 16) In VSMCs, the addition of DHA at the time of agonist stimulation has no effect on intracellular Ca 2+ mobilization, even in the presence of extracellular Ca 2+ . 5) Therefore, the inhibitory effect of DHA on SOCE may depend on cell type, being different between vascular and other cell types.…”

The necessity of adequate nutrition with diets containing omega-3 and omega-6 fatty acids for proper brain development, function and delayed aging: Review

“…PUFA act by participating in the control of many various metabolic mechanisms like regulation of calcium levels in astrocytes (Sergeeva et al, 2005). It has also been shown that phospholipases A2, C, and D are important participants in the signaling and interplay of different metabolic and signal pathways in LA-N-1 cell nuclei (Farooqui and Horrocks, 2005).…”