Roscovitine increases intracellular calcium release and capacitative calcium entry in PC12 cells.
Cyclin-dependent kinase 5 (Cdk5), which is activated by the non-cyclin regulator p35 or p39, is a proline-directed serine/threonine kinase that is implicated in many physiological and pathological processes. Here, we studied calcium signaling using the fluorescent cytosolic calcium indicator, Fura-4, in NGF-differentiated PC12 cells treated with roscovitine, a Cdk5 inhibitor. As compared to the control cells, the roscovitine-treated cells significantly potentiated intracellular calcium release by membrane depolarization (high K(+)) or through thapsigargin. In addition, roscovitine increased the magnitude of capacitative calcium entry (CCE), i.e., a calcium influx mechanism triggered by the depletion of intracellular calcium stores. Notably, roscovitine markedly slowed the rate of Ca(2+) removal from the plasma membrane. These results suggest that Cdk5 regulates intracellular calcium homeostasis and that the dysregulation of Cdk5 may contribute to disease pathogenesis by perturbing cellular Ca(2+) signaling.
Choi
Ho Sook
HS
Graduate Program in Neuroscience, Institute for Brain Science and Technology, Inje University, 633-146 Gaegeum 2-dong, Busanjin-gu, Busan 614-735, South Korea.
Chung
Sul-Hee
SH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002454:Cell Differentiation; D051360:Cyclin-Dependent Kinase 5 / Q000037:antagonists & inhibitors*; D042541:Intracellular Space / Q000378:metabolism; D007701:Kinetin / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000494:pharmacology; D016716:PC12 Cells; D011687:Purines / Q000494:pharmacology*; D051381:Rats; D000077546:Roscovitine
D011687:Purines; D000077546:Roscovitine; C090046:olomoucine; D020932:Nerve Growth Factor; D051360:Cyclin-Dependent Kinase 5; C495907:Cdk5 protein, rat; D007701:Kinetin; D002118:Calcium