NF-κB-Dependent Upregulation of NCX1 Induced by Angiotensin II Contributes to Calcium Influx in Rat Aortic Smooth Muscle Cells

Liu, Bei; Yang, Lixia; Zhang, Bin; Kuang, Chenwei; Huang, Songquan; Guo, R. S.

doi:10.1016/j.cjca.2016.02.060

Cited by 7 publications

(5 citation statements)

References 30 publications

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“…NCX1 was previously thought to function in the Ca 2+ exit mode to extrude the elevated [Ca 2+ ] cyt after cell activation. However, recent studies indicate that it also functions in the Ca 2+ entry mode under physiological conditions . Applying genetic knockdown of NCX1in the EMN, we showed that the amplitude of neuronal response to hypotonic stretch was reduced and the time course of response was delayed after NCX1 knockdown (compare Figure A vs B), suggesting that both Ca 2+ transport capacity and rate of NCX1 were decreased.…”

Section: Discussionmentioning

confidence: 75%

“…However, recent studies indicate that it also functions in the Ca 2+ entry mode under physiological conditions. 50,51 Applying genetic knockdown of NCX1in the EMN, we showed that the amplitude of neuronal response to hypotonic stretch was reduced and the time course of response was delayed after NCX1 knockdown (compare Figure 2A vs 2B), suggesting that both Ca 2+ transport capacity and rate of NCX1 were decreased. Our results support an important role of NCX1 in the Ca 2+ entry mode in the mechanosensitivity of EMNs.…”

Section: F I G U R E 6 Immunocytochemistrymentioning

confidence: 96%

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Na⁺/Ca²⁺ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons

et al. 2018

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Aim: Our earlier studies showed that mechanical stretch activates inhibitory motor neurons of the oesophagus; however, the underlying molecular mechanisms are unclear. Here, we sought to examine if Na + /Ca 2+ exchanger 1 (NCX1) is responsible for the mechanosensitivity in the esophageal myenteric neurons (EMN) of rats and humans. Methods: The function of NCX1 in primary culture of neurons was determined using calcium imaging, and mechanosensitivity was tested using osmotic stretch and direct mechanical stretch. Axial stretch-induced relaxation of the lower esophageal sphincter (LES) was also studied in vivo in rats. Results: The expression and co-localization of NCX1 with nNOS were identified in the EMN from both rats and humans. The extracellular Ca 2+ entry caused by ATP through purinergic signalling in the rat EMN was significantly inhibited by selective NCX blockers. Removal of extracellular Na + to activate the Ca 2+ entry mode of NCX1 induced an increase in the cytoplasmic calcium ([Ca 2+ ] cyt ), which was attenuated by NCX blockers. Osmotic stretch and mechanical stretch-induced [Ca 2+ ] cyt signalling in the rat and human EMN were attenuated by NCX blockers as well as specific NCX1 knockdown. Osmotic stretch and mechanical stretch also induced [Ca 2+ ] cyt signalling in the Chinese hamster ovary (CHO) cells with NCX1 over-expression, which was attenuated by NCX blockers. Finally, NCX blockade inhibited axial stretch-activated LES relaxation in vivo experiments in the rats. Conclusions:We demonstrate a novel NCX1/Ca 2+ pathway in the mechanosensitive neurons of rat and human oesophagus, which may provide a potential therapeutic target for the treatment of oesophageal motility disorders. K E Y W O R D Sesophageal myenteric neurons, lower esophageal sphincter relaxation, mechanosensitive neurons, Na +/ Ca 2+ exchanger 1

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Section: Discussionmentioning

confidence: 75%

Section: F I G U R E 6 Immunocytochemistrymentioning

confidence: 96%

Na⁺/Ca²⁺ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons

et al. 2018

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“…Although the precise mechanism by which the reverse mode of NCX is activated by 5-HT is still unclear, it was reported recently that the reverse mode of NCX1 contributes to angiotensin II-induced Ca 2+ influx in VSMCs. 23) The authors made the point that angiotensin II-induced SOCE may increase the concentration of intracellular Na + through mechanisms involving the TRPC family, and this intracellular Na + may lead to the activation of the reverse mode of NCX. Therefore, the suppression of NCX1 expression by DHA treatment may con- tribute to the inhibition of Ca 2+ influx in VSMCs.…”

Section: Discussionmentioning

confidence: 99%

Effect of Docosahexaenoic Acid on Voltage-Independent Ca<sup>2+</sup> Entry Pathways in Cultured Vascular Smooth Muscle Cells Stimulated with 5-Hydroxytryptamine

Machida

Onoguchi

Iizuka

et al. 2017

Biological & Pharmaceutical Bulletin

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“…The role of SERCA (Zhang et al, 2018;Pereira et al, 2022); PMCA (Pande et al, 2006;Baryshnikov et al, 2009) and NCX (Liu et al, 2016;Yang et al, 2020) in clearing cytosolic Ca 2+ upon agonist stimulation in aortic VSMCs has extensively been reported. However, few studies are available above the effect of DM on the activity of these Ca 2+clearing mechanisms VSMCs.…”

Section: T2dm Shortens the Early Phase Of The Decay And Increases The...mentioning

confidence: 99%

“…In accord, the Mn 2+ -quenching assay confirmed that extracellular Ca 2+ entry evoked by the pharmacological depletion of the ER Ca 2+ store with CPA was remarkably larger in OZDF VSMCs as compared to LZDF. However, the increase in plateau amplitude could also reflect a reduction in the activity of Ca 2+ -extruding mechanisms and/or an increase in Ca 2+ entry through the reverse mode of NCX (Zhang et al, 2005;Pulina et al, 2010;Liu et al, 2016;Berra-Romani et al, 2019).…”

Section: T2dm Shortens the Early Phase Of The Decay And Increases The...mentioning

confidence: 99%

Alterations of the Ca2+ clearing mechanisms by type 2 diabetes in aortic smooth muscle cells of Zucker diabetic fatty rat

Moreno-Salgado,

Coyotl-Santiago,

Moreno-Vazquez

et al. 2023

Front. Physiol.

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Type 2 Diabetes Mellitus (T2DM) is a rapidly rising disease with cardiovascular complications constituting the most common cause of death among diabetic patients. Chronic hyperglycemia can induce vascular dysfunction through damage of the components of the vascular wall, such as vascular smooth muscle cells (VSMCs), which regulate vascular tone and contribute to vascular repair and remodeling. These functions are dependent on intracellular Ca2+ changes. The mechanisms by which T2DM affects Ca2+ handling in VSMCs still remain poorly understood. Therefore, the objective of this study was to determine whether and how T2DM affects Ca2+ homeostasis in VSMCs. We evaluated intracellular Ca2+ signaling in VSMCs from Zucker Diabetic Fatty rats using Ca2+ imaging with Fura-2/AM. Our results indicate that T2DM decreases Ca2+ release from the sarcoplasmic reticulum (SR) and increases the activity of store-operated channels (SOCs). Moreover, we were able to identify an enhancement of the activity of the main Ca2+ extrusion mechanisms (SERCA, PMCA and NCX) during the early stage of the decay of the ATP-induced Ca2+ transient. In addition, we found an increase in Ca2+ entry through the reverse mode of NCX and a decrease in SERCA and PMCA activity during the late stage of the signal decay. These effects were appreciated as a shortening of ATP-induced Ca2+ transient during the early stage of the decay, as well as an increase in the amplitude of the following plateau. Enhanced cytosolic Ca2+ activity in VSMCs could contribute to vascular dysfunction associated with T2DM.

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NF-κB-Dependent Upregulation of NCX1 Induced by Angiotensin II Contributes to Calcium Influx in Rat Aortic Smooth Muscle Cells

Cited by 7 publications

References 30 publications

Na⁺/Ca²⁺ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons

Na⁺/Ca²⁺ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons

Effect of Docosahexaenoic Acid on Voltage-Independent Ca<sup>2+</sup> Entry Pathways in Cultured Vascular Smooth Muscle Cells Stimulated with 5-Hydroxytryptamine

Alterations of the Ca2+ clearing mechanisms by type 2 diabetes in aortic smooth muscle cells of Zucker diabetic fatty rat

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NF-κB-Dependent Upregulation of NCX1 Induced by Angiotensin II Contributes to Calcium Influx in Rat Aortic Smooth Muscle Cells

Cited by 7 publications

References 30 publications

Na+/Ca2+ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons

Na+/Ca2+ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons

Effect of Docosahexaenoic Acid on Voltage-Independent Ca<sup>2+</sup> Entry Pathways in Cultured Vascular Smooth Muscle Cells Stimulated with 5-Hydroxytryptamine

Alterations of the Ca2+ clearing mechanisms by type 2 diabetes in aortic smooth muscle cells of Zucker diabetic fatty rat

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Na⁺/Ca²⁺ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons

Na⁺/Ca²⁺ exchanger 1 is a key mechanosensitive molecule of the esophageal myenteric neurons