Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

Wang, Rui Xing; He, Rui; Jiao, Hai Xia; Dai, Mao; Mu, Yun Ping; Hu, Ying; Wu, Zhi; Sham, James S.K.; Lin, Mo Jun

doi:10.1159/000373966

Cited by 30 publications

(50 citation statements)

References 70 publications

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“…Given more ET-1 produced at the renal tubular epithelial cells than any other cell type [14,15], we hypothesis that CPU0213 inhibits apoptosis in renal tubular epithelial cells. To test this hypothesis, the present study used human renal tubular epithelial cell line (HK-2) to test the role of CPU0213 on apoptosis by Western blot analysis and flow cytometer.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

Shao

et al. 2016

Cell Physiol Biochem

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Background/Aims: Our previous studies have indicated that a novel endothelin receptor antagonist CPU0213 effectively normalized renal function in diabetic nephropathy. However, the molecular mechanisms mediating the nephroprotective role of CPU0213 remain unknown. Methods and Results: In the present study, we first detected the role of CPU0213 on apoptosis in human renal tubular epithelial cell (HK-2). It was shown that high glucose significantly increased the protein expression of Bax and decreased Bcl-2 protein in HK-2 cells, which was reversed by CPU0213. The percentage of HK-2 cells that showed Annexin V-FITC binding was markedly suppressed by CPU0213, which confirmed the inhibitory role of CPU0213 on apoptosis. Given the regulation of endothelin (ET) system to oxidative stress, we determined the role of redox signaling in the regulation of CPU0213 on apoptosis. It was demonstrated that the production of superoxide (O₂^-.) was substantially attenuated by CPU0213 treatment in HK-2 cells. We further found that CPU0213 dramatically inhibited expression of Nox4 protein, which gene silencing mimicked the role of CPU0213 on the apoptosis under high glucose stimulation. We finally examined the role of CPU0213 on ET-1 receptors and found that high glucose-induced protein expression of endothelin A and B receptors was dramatically inhibited by CPU0213. Conclusion: Taken together, these results suggest that this Nox4-dependenet O₂^- production is critical for the apoptosis of HK-2 cells in high glucose. Endothelin receptor antagonist CPU0213 has an anti-apoptosis role through Nox4-dependent O₂^-.production, which address the nephroprotective role of CPU0213 in diabetic nephropathy.

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Section: Introductionmentioning

confidence: 99%

Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

Shao

et al. 2016

Cell Physiol Biochem

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“…The monocrotaline (MCT) model was established using a single intraperitoneal injection of MCT (50 mg/kg) into male Sprague-Dawley (SD) rats (140 -150 g). The chronic hypoxic (CH) model was developed and characterized as previously described [26,27]. Adult agematched male SD rats (200 -250 g) were used as normal controls for all models of PH.…”

Section: Animal Models Of Phmentioning

confidence: 99%

“…Standard SDS-PAGE electrophoresis (12% gels) with transfer to a PVDF membrane was used [26,27]. Membranes were incubated overnight at 4°C with a polyclonal rabbit anti-Cav-1 (1:5000; Cell Signaling Technology), anti-TRPC1 or anti-TRPC6 (1:300; Abcam), or β-actin (1:5000; Cell Signaling Technology) antibodies.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Published by S. Karger AG, Basel www.karger.com/cpb endothelium was disrupted as described previously [26,27]. A pH of 7.4 (adjusted with NaOH) was maintained in solution at a temperature of 37°C bubbled with 95% O 2 , and 5% CO 2 .…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

“…AoSMCs were isolated and cultured as previously described [26,27]. Briefly, rats were anesthetized with urethane (1 g/kg) and exsanguinated.…”

Section: Cell Isolation and Culturementioning

confidence: 99%

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Alterations in Caveolin-1 Expression and Receptor-Operated Ca2+ Entry in the Aortas of Rats with Pulmonary Hypertension

Mu¹,

Lin²,

Yan³

et al. 2016

Cell Physiol Biochem

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Background/Aims: Alterations in intracellular Ca²⁺ concentration ([Ca²⁺]_i) underlie the pathogenesis of various cardiovascular diseases. Caveolin-1 (Cav-1) is the primary functional protein associated with caveolae, which are invaginations in the plasma membrane, and is a regulator of [Ca²⁺]_i signaling. Caveolae and Cav-1 increase the activity of store-operated Ca²⁺ channels (SOCC) in rat pulmonary arterial smooth muscle cells (PASMCs), and these enhancing effects were more pronounced in rats with pulmonary hypertension (PH). Classical transient receptor potential (TRPC) proteins are highly expressed in vascular smooth muscle cells, and these proteins form functional receptor-operated Ca²⁺ channels (ROCC) and SOCC in PASMCs. Previous studies suggested that functional and structural changes in aortas might occur during the pathological process of PH. Our data demonstrated that Cav-1 and TRPC were also abundant in the aorta smooth muscle cells (AoSMCs) of PH rats. However, previous PH research primarily focused on Ca²⁺ channels in pulmonary arteries, but not functional changes in Ca²⁺ channels in aortas. The contribution of Cav-1 of AoSMCs to alterations of Ca²⁺ signaling in aortic functions during the pathological process of PH has not been fully characterized. Therefore, this study investigated alterations in Cav-1 expression and the relationship of these changes to Ca²⁺ channels in AoSMCs of PH rats. Methods: The present study examined physiological caveolae and Cav-1 expression and characterized the function of altered Cav-1 expression in rat aortas with PH. Results: The appearance of caveolae with Cav-1 expression increased significantly in the aortas of rats with PH, but TRPC1 and TRPC6 expression was not altered. In vitro experiments demonstrated that caveolae contributed to phenylephrine, endothelin-1, and 1-oleoyl-2-acetyl-sn-glycerol (OAG)-induced aortic vasoreactivity, but KCl and cyclopiazonic acid had no effect, which suggests the vital ability of Cav-1 to regulate ROCC activity. The introduction of Cav-1 scaffolding domain peptide enhanced OAG-induced ROCC function in primary AoSMCs. Conclusion: Cav-1 is specifically associated with ROCC in aortas and plays a vital role in altering vasoreactivity, which affects cardiovascular diseases pathology. Caveolae and Cav-1 up-regulation may affect the function of ROCC in rat models of PH.

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Ginseng in vascular dysfunction: A review of therapeutic potentials and molecular mechanisms

Zhang

Xue

et al. 2022

Phytotherapy Research

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Vascular dysfunction can lead to a variety of fatal diseases, including cardiovascular and cerebrovascular diseases, metabolic syndrome, and cancer. Although a large number of studies have reported the therapeutic effects of natural compounds on vascular-related diseases, ginseng is still the focus of research. Ginseng and its active substances have bioactive effects against different diseases with vascular dysfunction. In this review, we summarized the key molecular mechanisms and signaling pathways of ginseng, its different active ingredients or formula in the prevention and treatment of vascular-related diseases, including cardiac-cerebral vascular diseases, hypertension, diabetes complications, and cancer. Moreover, the bidirectional roles of ginseng in promoting or inhibiting angiogenesis have been highlighted. We systematically teased out the relationship between ginseng and vascular dysfunction, which could provide a basis for the clinical application of ginseng in the future.

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Ginsenoside Rb1 Attenuates Agonist-Induced Contractile Response via Inhibition of Store-Operated Calcium Entry in Pulmonary Arteries of Normal and Pulmonary Hypertensive Rats

Cited by 30 publications

References 70 publications

Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

Inhibition of CPU0213, a Dual Endothelin Receptor Antagonist, on Apoptosis via Nox4-Dependent ROS in HK-2 Cells

Alterations in Caveolin-1 Expression and Receptor-Operated Ca2+ Entry in the Aortas of Rats with Pulmonary Hypertension

Ginseng in vascular dysfunction: A review of therapeutic potentials and molecular mechanisms

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