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|Title:||Phospholipase C-γ1 is required for the activation of store-operated Ca²⁺ channels in liver cells|
|Other Titles:||Phospholipase C-gamma1 is required for the activation of store-operated Ca(2+) channels in liver cells|
Castro Kraftchenko, J.
|Citation:||Biochemical Journal, 2007; 405(2):269-276|
|Tom Litjens, Than Nguyen, Joel Castro, Edoardo C. Aromataris, Lynette Jones, Greg J. Barritt And Grigori Y. Rychkov|
|Abstract:||Repetitive hormone-induced changes in concentration of free cytoplasmic Ca2+ in hepatocytes require Ca2+ entry through receptor-activated Ca2+ channels and SOCs (store-operated Ca2+ channels). SOCs are activated by a decrease in Ca2+ concentration in the intracellular Ca2+ stores, but the molecular components and mechanisms are not well understood. Some studies with other cell types suggest that PLC-gamma (phospholipase C-gamma) is involved in the activation of receptor-activated Ca2+ channels and/or SOCs, independently of PLC-gamma-mediated generation of IP3 (inositol 1,4,5-trisphosphate). The nature of the Ca2+ channels regulated by PLC-gamma has not been defined clearly. The aim of the present study was to determine if PLC-gamma is required for the activation of SOCs in liver cells. Transfection of H4IIE cells derived from rat hepatocytes with siRNA (short interfering RNA) targeted to PLC-gamma1 caused a reduction (by approx. 70%) in the PLC-gamma1 protein expression, with maximal effect at 72-96 h. This was associated with a decrease (by approx. 60%) in the amplitude of the I(SOC) (store-operated Ca2+ current) developed in response to intracellular perfusion with either IP(3) or thapsigargin. Knockdown of STIM1 (stromal interaction molecule type 1) by siRNA also resulted in a significant reduction (approx. 80% at 72 h post-transfection) of the I(SOC) amplitude. Immunoprecipitation of PLC-gamma1 and STIM1, however, suggested that under the experimental conditions these proteins do not interact with each other. It is concluded that the PLC-gamma1 protein, independently of IP3 generation and STIM1, is required to couple endoplasmic reticulum Ca2+ release to the activation of SOCs in the plasma membrane of H4IIE liver cells.|
RNA, Small Interfering
Phospholipase C gamma
Stromal Interaction Molecule 1
|Rights:||Copyright © 2007 Biochemical Society|
|Appears in Collections:||Aurora harvest|
Molecular and Biomedical Science publications
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