Glucose elevations alter bradykinin-stimulated intracellular calcium accumulation in cultured endothelial cells

Pieper, Galen M.; Dondlinger, L. A.

doi:10.1016/s0008-6363(97)00007-2

Cited by 29 publications

(29 citation statements)

References 37 publications

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“…However, the results of these studies are not consistent. In porcine aortic endothelial cells, 1 day of culture with high glucose (44 mmol/l) caused enhanced increases in [Ca 2+ ] i in response to bradykinin [7,22], whereas an opposing effect was observed in another study when BAECs were exposed to 25 mmol/l glucose for 24 h [23]. In our study, 2 days of culture in high glucose did not affect bradykinin-induced increases in [Ca 2+ ] i in endothelial cells.…”

Section: Discussioncontrasting

confidence: 66%

“…A few studies on cultured endothelial cells at high glucose for a short period (up to 2 days) have revealed alterations in [Ca 2+ ] i homeostasis [7,22,23]. However, the results of these studies are not consistent.…”

Section: Discussionmentioning

confidence: 95%

“…The reduction in NO formation in endothelial cells from diabetic individuals could occur at one or several intervals in this pathway. Although a few studies in cultured cells at different concentrations of high glucose for a short term (1-2 days) found alterations in [Ca 2+ ] i responses and NO formation, the resulting data are conflicting and are not conclusive [7,22,23]. Furthermore, little is known about the long-term effect of high glucose on the PLC-mediated signalling pathway.…”

Section: Introductionmentioning

confidence: 99%

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Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C

Tang

2004

Diabetologia

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Aims/hypothesis. Overwhelming evidence indicates that endothelial cell dysfunction in diabetes is characterised by diminished endothelium-dependent relaxation, but the matter of the underlying molecular mechanism remains unclear. As nitric oxide (NO) production from the endothelium is the major player in endothelium-mediated vascular relaxation, we investigated the effects of high glucose on NO production, and the possible alterations of signalling pathways implicated in this scenario. Methods. NO production and intracellular Ca 2+ levels ([Ca 2+ ] i ) were assessed using the fluorescent probes 4,5-diaminofluorescein diacetate and fura-2 respectively. Results. Exposure of cultured bovine aortic endothelial cells to high glucose for 5 or 10 days significantly reduced NO production induced by bradykinin (but not by Ca 2+ ionophore) in a time-and dose-dependent manner. This was probably due to an attenuation in bradykinin-induced elevations of [Ca 2+ ] i under these conditions, since a close correlation between [Ca 2+ ] i increases and NO generation was observed in intact bovine aortic endothelial cells. Both bradykinin-promoted intracellular Ca 2+ mobilisation and extracellular Ca 2+ entry were affected. Moreover, bradykinin-induced formation of Ins(1,4,5)P 3 , a phospholipase C product leading to increases in [Ca 2+ ] i , was also inhibited following high glucose culture. This abnormality was not attributable to a decrease in inositol phospholipids, but possibly to a reduction in the number of bradykinin receptors. The alterations in NO production, the increases in [Ca 2+ ] i , and the bradykinin receptor number due to high glucose could be largely reversed by protein kinase C inhibitors and D-α-tocopherol (antioxidant). Conclusions/interpretation. Chronic exposure to high glucose reduces NO generation in endothelial cells, probably by impairing phospholipase-C-mediated Ca 2+ signalling due to excess protein kinase C activation. This defect in NO release may contribute to the diminished endothelium-dependent relaxation and thus to the development of cardiovascular diseases in diabetes.

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Section: Discussioncontrasting

confidence: 66%

Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C

Tang

2004

Diabetologia

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“…Notably, attenuation of Ca 2+ entry pathways has been frequently observed under pathological conditions (e.g. diabetes mellitus [43]), and thus pathologically altered Ca 2+ channel activity might contribute to protein misfolding in diseases.…”

Section: Discussionmentioning

confidence: 99%

Mitochondria maintain maturation and secretion of lipoprotein lipase in the endoplasmic reticulum

Osibow

Frank

Malli

et al. 2006

Biochemical Journal

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Considering the physiological Ca 2+ dynamics within the ER (endoplasmic reticulum), it remains unclear how efficient protein folding is maintained in living cells. Thus, utilizing the strictly folding-dependent activity and secretion of LPL (lipoprotein lipase), we evaluated the impact of ER Ca 2+ content and mitochondrial contribution to Ca 2+ -dependent protein folding. Exhaustive ER Ca 2+ depletion by inhibition of sarcoplasmic/ endoplasmic reticulum Ca 2+ -ATPases caused strong, but reversible, reduction of cell-associated and released activity of constitutive and adenovirus-encoded human LPL in CHO-K1 (Chinesehamster ovary K1) and endothelial cells respectively, which was not due to decline of mRNA or intracellular protein levels. In contrast, stimulation with the IP 3 (inositol 1,4,5-trisphosphate)-generating agonist histamine only moderately and transiently affected LPL maturation in endothelial cells that paralleled a basically preserved ER Ca 2+ content. However, in the absence of extracellular Ca 2+ or upon prevention of transmitochondrial Ca 2+ flux, LPL maturation discontinued upon histamine stimulation. Collectively, these data indicate that Ca 2+ -dependent protein folding in the ER is predominantly controlled by intraluminal Ca 2+ and is largely maintained during physiological cell stimulation owing to efficient ER Ca 2+ refilling. Since Ca 2+ entry and mitochondrial Ca 2+ homoeostasis are crucial for continuous Ca 2+ -dependent protein maturation in the ER, their pathological alterations may result in dysfunctional protein folding.

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“…Notably, endothelial Ca 2+ signalling has been shown to be a suitable marker for cell dysfunction initiated by a variety of stimuli such as E. coli lipopolysaccharides (LPS; [19]), peroxides [20,21,22], oxidized low density lipoprotein [23], streptozotocininduced diabetes [24,25] and hyperglycaemia [10,11,26]. The latter was causally linked to generation of · O 2 -in EC [10,27].…”

Section: Discussionmentioning

confidence: 99%

Intercellular signalling within vascular cells under high D-glucose involves free radical-triggered tyrosine kinase activation

et al. 2003

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Aims/hypothesis. Diabetes mellitus is associated with endothelial dysfunction in human arteries due to the release of superoxide anions ( · O 2 -) that was found to occur predominantly in smooth muscle cells (SMC). This study was designed to elucidate the impact of high glucose concentration mediated radical production in SMC on EC. Pre-treatment of vascular SMC with increased D-glucose enhanced release of · O 2 -. Methods. Microscope-based analyses of intracellular free Ca 2+ concentration (fura-2), immunohistochemistry (f-actin) and tyrosine kinase activity were performed. Furthermore, RT-PCR and Western blots were carried out. Results. Interaction of EC with SMC pre-exposed to high glucose concentration yielded changes in endothelial Ca 2+ signalling and polymerization of f-actin in a concentration-dependent and superoxide dismutase (SOD) sensitive manner. This interaction activated endothelial tyrosine kinase(s) but not NFκB and AP-1, while SOD prevented tyrosine kinase stimulation but facilitated NFκB and AP-1 activation. Erbstatin, herbimycin A and the src family specific kinase inhibitor PP-1 but not the protein kinase C inhibitor GF109203X prevented changes in endothelial Ca 2+ signalling and cytoskeleton organization induced by pre-exposure of SMC to high glucose concentration. Adenovirus-mediated expression of kinase-inactive c-src blunted the effect of pre-exposure of SMC to high glucose concentration on EC. Conclusions/interpretation. These data suggest that SMC-derived · O 2 -alter endothelial cytoskeleton organization and Ca 2+ signalling via activation of c-src. The activation of c-src by SMC-derived radicals is a new concept of the mechanisms underlying vascular dysfunction in diabetes. [Diabetologia (2003) 46:773-783]

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Glucose elevations alter bradykinin-stimulated intracellular calcium accumulation in cultured endothelial cells

Abstract: Hyperglycemia may contribute to defective endothelium-dependent relaxation in diabetes via an attenuated increase in Ca2+i signal transduction for the release of nitric oxide by endothelial cells. This defect possibly arises as a consequence of hydroxyl radicals formed intracellularly.

Cited by 29 publications

References 37 publications

Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C

Chronic exposure to high glucose impairs bradykinin-stimulated nitric oxide production by interfering with the phospholipase-C-implicated signalling pathway in endothelial cells: evidence for the involvement of protein kinase C

Mitochondria maintain maturation and secretion of lipoprotein lipase in the endoplasmic reticulum

Intercellular signalling within vascular cells under high D-glucose involves free radical-triggered tyrosine kinase activation

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