Initial bradykinin triggers calcium-induced calcium release in C6 glioma cells and its significance

Abstract

Objective To investigate the underlying mechanism for the selective modulation of the permeability of blood-tumor barrier (BTB) by small dose of bradykinin (BK). Methods C6 glioma cells were treated with BK, and changes of intracellular nitric oxide (NO) and intracellular calcium level were measured with fluorescent spectrophotometer. Results The initial application of BK easily triggered extracellular calcium influx, which resulted in intracellular calcium store release in C6 glioma cells.The above mechanism was also named ryanodine mediated calcium induced calcium release (CICR). We also detected a longlasting intracellular NO elevation in C6 glioma cells upon BK treatment. Further study showed that ryanodine mediated CICR contributed greatly to the secondary NO elevation induced by BK treatment. Conclusion These results suggested that BK triggered CICR in C6 glioma cells and the associated NO generation might be the underlying mechanism for the selective modulation of BTB permeability by BK.

RETRACTED: The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB

“…Due to the presence of blood tumor barrier (BTB), macromolecular chemotherapeutic agents are arduous to reach the tumor tissues and dramatically attenuate the chemotherapeutic effect. Accordingly, selective BTB opening is an effective method to improve chemotherapeutic efficacy of brain glioma (Black and Ningaraj, 2004 ; Wang and Liu, 2009 ; Wang et al, 2015 ).…”

Bradykinin‐mediated Ca2+ signalling regulates cell growth and mobility in human cardiac c‐Kit+ progenitor cells

“…In rat C6 glioma cells, bradykinin triggers Ca 2+ influx, resulting in calcium store Ca 2+ release, which is associated with nitric oxide generation for regulating permeability of blood‐tumour barrier,43 while in primary cultured rat brain microvascular endothelial cells, bradykinin‐triggered Ca 2+ influx‐induced Ca 2+ release is involved in regulation of the junction protein claudin‐5 19. A recent study shows that Ca 2+ signalling induced by bradykinin results from initial Ca 2+ release from ER IP3Rs followed by Ca 2+ entry through Ca 2+ release‐activated channels in normal pancreatic stellate cells 44.…”

“…41 However, an earlier study demonstrated that bradykinin induces an increase in inositol 1,4,5-triphosphate (IP3) in neonatal rat cardiomyocytes 42 and bradykinin-mediated short nocifensive responses is related to activating PLC, followed by Orai1 in afferent sensory neurons. 18 In rat C6 glioma cells, bradykinin triggers Ca 2+ influx, resulting in calcium store Ca 2+ release, which is associated with nitric oxide generation for regulating permeability of blood-tumour barrier, 43 while in primary cultured rat brain microvascular endothelial cells, bradykinin-triggered Ca 2+ influx-induced Ca 2+ release is involved in regulation of the junction protein claudin-5. 19 A recent study shows that Ca 2+ signalling induced by bradykinin results from initial Ca 2+ release from ER IP3Rs followed by Ca 2+ entry through Ca 2+ release-activated channels in normal pancreatic stellate cells.…”