Pharmacological characterization of the involvement of protein kinase C in oscillatory and non-oscillatory calcium increases in astrocytes

Abstract

Evidence increasingly shows that astrocytes play a pivotal role in brain physiology and pathology via calcium dependent processes, thus the characterization of the calcium dynamics in astrocytes is of growing importance. We have previously reported that the epidermal growth factor and basic fibroblast growth factor up-regulate the oscillation of the calcium releases that are induced by stimuli, including glutamate in cultured astrocytes. This calcium oscillation is assumed to involve protein kinase C (PKC), which is activated together with the calcium releases as a consequence of inositol phospholipid hydrolysis. In the present study, this issue has been investigated pharmacologically by using astrocytes cultured with and without the growth factors. The pharmacological activation of PKC largely reduced the glutamate-induced oscillatory and non-oscillatory calcium increases. Meanwhile, PKC inhibitors increased the total amounts of both calcium increases without affecting the peak amplitudes and converted the calcium oscillations to non-oscillatory sustained calcium increases by abolishing the falling phases of the repetitive calcium increases. Furthermore, the pharmacological effects were consistent between both glutamate- and histamine-induced calcium oscillations. These results suggest that PKC up-regulates the removal of cytosolic calcium in astrocytes, and this up-regulation is essential for calcium oscillation in astrocytes cultured with growth factors.

PKC epsilon‐dependent calcium oscillations associated with metabotropic glutamate receptor 5 prevent agonist‐mediated receptor desensitization in astrocytes

“…These observations are consistent with the data reported by Morita et al . () showing that inhibition of PKC by a series of pharmacological inhibitors converts astrocytic calcium signalling from an oscillatory to a sustained or non‐oscillatory calcium response (Morita et al . ).…”

“…() showing that inhibition of PKC by a series of pharmacological inhibitors converts astrocytic calcium signalling from an oscillatory to a sustained or non‐oscillatory calcium response (Morita et al . ). Moreover, cells exposed to a selective PKCε activator also showed a loss of calcium oscillations and exhibited progressive desensitization.…”

Multiple calcium patterns of rat osteoblasts under fluidic shear stress

“…With Fss increased, [Ca 2+ ] i patterns changed from perfection oscillations, to combined oscillations at the plateau, and to homogeneous peak‐plateau patterns. Biochemical stimuli could result in similar phenomena, suggesting that strong stimuli leaded to more non‐oscillatory [Ca 2+ ] i increase while slight stimuli induced more [Ca 2+ ] i oscillations, such as in ATP‐stimulated Hela cells and glutamate‐stimulated astrocytes . Cell density also contributed to [Ca 2+ ] i patterns that high cell density increased [Ca 2+ ] i oscillations in non‐excitable cells .…”

Constitutive downregulation protein kinase C epsilon in hSOD1G93A astrocytes influences mGluR5 signaling and the regulation of glutamate uptake

“…Morita et al have shown that blockade of PKCs by a series of pharmacological inhibitors converts glutamate-induced Ca 21 oscillations to sustained or nonoscillatory responses in astrocytes (Morita, Nakane, Maekawa, & Kudo, 2015). Morita et al have shown that blockade of PKCs by a series of pharmacological inhibitors converts glutamate-induced Ca 21 oscillations to sustained or nonoscillatory responses in astrocytes (Morita, Nakane, Maekawa, & Kudo, 2015).…”

“…The mobilization of Ca 21 by mGluR5 is largely dependent on the initial release of Ca 21 from intracellular stores, suggesting that downstream signaling effectors of mGluR5 could be implicated in the altered mGluR5 signaling in hSOD1 G93A astrocytes. Morita et al have shown that blockade of PKCs by a series of pharmacological inhibitors converts glutamate-induced Ca 21 oscillations to sustained or nonoscillatory responses in astrocytes (Morita, Nakane, Maekawa, & Kudo, 2015). More specifically, reduced expression of the PKCE isoform has been shown to convert the mGluR5 oscillatory profile into a peakplateau type response (Bradley & Challiss, 2011;Vergouts et al, 2017).…”