期刊
TOXINS
卷 13, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/toxins13010020
关键词
astrocytes; A946; 8211; 42 oligomers; BDS-I; [Ca transients; ER stress; K3; 4 channel
资金
- Progetto Ateneo Federico II
- Progetto Speciale di Ateneo [CA.04_CDA_n_103]
The marine toxin BDS-I was found to improve [Ca2+](i) transients in rat primary cortical astrocytes exposed to A beta(1-42) oligomers by affecting K(V)3.4 channels, thereby preventing A beta(1-42)-induced ER stress and cell suffering.
Intracellular calcium concentration ([Ca2+](i)) transients in astrocytes represent a highly plastic signaling pathway underlying the communication between neurons and glial cells. However, how this important phenomenon may be compromised in Alzheimer's disease (AD) remains unexplored. Moreover, the involvement of several K+ channels, including K(V)3.4 underlying the fast-inactivating currents, has been demonstrated in several AD models. Here, the effect of K(V)3.4 modulation by the marine toxin blood depressing substance-I (BDS-I) extracted from Anemonia sulcata has been studied on [Ca2+](i) transients in rat primary cortical astrocytes exposed to A beta(1-42) oligomers. We showed that: (1) primary cortical astrocytes expressing K(V)3.4 channels displayed [Ca2+](i) transients depending on the occurrence of membrane potential spikes, (2) BDS-I restored, in a dose-dependent way, [Ca2+](i) transients in astrocytes exposed to A beta(1-42) oligomers (5 mu M/48 h) by inhibiting hyperfunctional K(V)3.4 channels, (3) BDS-I counteracted Ca2+ overload into the endoplasmic reticulum (ER) induced by A beta(1-42) oligomers, (4) BDS-I prevented the expression of the ER stress markers including active caspase 12 and GRP78/BiP in astrocytes treated with A beta(1-42) oligomers, and (5) BDS-I prevented A beta(1-42)-induced reactive oxygen species (ROS) production and cell suffering measured as mitochondrial activity and lactate dehydrogenase (LDH) release. Collectively, we proposed that the marine toxin BDS-I, by inhibiting the hyperfunctional K(V)3.4 channels and restoring [Ca2+](i) oscillation frequency, prevented A beta(1-42)-induced ER stress and cell suffering in astrocytes.
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