Multifunctional Liposomes Modulate Purinergic Receptor-Induced Calcium Wave in Cerebral Microvascular Endothelial Cells and Astrocytes: New Insights for Alzheimer’s disease
| Autor: | Giulio Sancini, Dmitry Lim, Greta Forcaia, Francesco Moccia, Giulia Terribile, Francesca Re, Gerardo Biella, Beatrice Formicola, Sharon Negri |
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| Přispěvatelé: | Forcaia, G, Formicola, B, Terribile, G, Negri, S, Lim, D, Biella, G, Re, F, Moccia, F, Sancini, G |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
P2Y receptor Indoles SERCA Neuroscience (miscellaneous) Phosphatidic Acids Endoplasmic Reticulum Article Calcium in biology Cell Line Sarcoplasmic Reticulum Calcium-Transporting ATPases 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Adenosine Triphosphate 0302 clinical medicine Intracellular calcium waves BIO/09 - FISIOLOGIA Alzheimer Disease Animals Humans Calcium Signaling Chemistry Purinergic receptor Receptors Purinergic Brain Endothelial Cells Purinergic signalling Rats Cell biology Liposome Calcium ATPase 030104 developmental biology Neurology Astrocytes Liposomes Microvessels Calcium Purinergic receptors Cyclopiazonic acid Alzheimer’s disease 030217 neurology & neurosurgery Intracellular Intracellular calcium wave |
| Zdroj: | Molecular Neurobiology |
| ISSN: | 1559-1182 0893-7648 |
| DOI: | 10.1007/s12035-021-02299-9 |
| Popis: | In light of previous results, we assessed whether liposomes functionalized with ApoE-derived peptide (mApoE) and phosphatidic acid (PA) (mApoE-PA-LIP) impacted on intracellular calcium (Ca2+) dynamics in cultured human cerebral microvascular endothelial cells (hCMEC/D3), as an in vitro human blood-brain barrier (BBB) model, and in cultured astrocytes. mApoE-PA-LIP pre-treatment actively increased both the duration and the area under the curve (A.U.C) of the ATP-evoked Ca2+ waves in cultured hCMEC/D3 cells as well as in cultured astrocytes. mApoE-PA-LIP increased the ATP-evoked intracellular Ca2+ waves even under 0 [Ca2+]e conditions, thus indicating that the increased intracellular Ca2+ response to ATP is mainly due to endogenous Ca2+ release. Indeed, when Sarco-Endoplasmic Reticulum Calcium ATPase (SERCA) activity was blocked by cyclopiazonic acid (CPA), the extracellular application of ATP failed to trigger any intracellular Ca2+ waves, indicating that metabotropic purinergic receptors (P2Y) are mainly involved in the mApoE-PA-LIP-induced increase of the Ca2+ wave triggered by ATP. In conclusion, mApoE-PA-LIP modulate intracellular Ca2+ dynamics evoked by ATP when SERCA is active through inositol-1,4,5-trisphosphate-dependent (InsP3) endoplasmic reticulum Ca2+ release. Considering that P2Y receptors represent important pharmacological targets to treat cognitive dysfunctions, and that P2Y receptors have neuroprotective effects in neuroinflammatory processes, the enhancement of purinergic signaling provided by mApoE-PA-LIP could counteract Aβ-induced vasoconstriction and reduction in cerebral blood flow (CBF). Our obtained results could give an additional support to promote mApoE-PA-LIP as effective therapeutic tool for Alzheimer’s disease (AD). |
| Databáze: | OpenAIRE |
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