Ginsenoside Rg-1 prevents elevated cytosolic Ca2+ via store-operated Ca2+ entry in high-glucose–stimulated vascular endothelial and smooth muscle cells

Han, A Young; Ha, Su Min; Shin, You Kyoung; Seol, Geun Hee

doi:10.1186/s12906-022-03647-5

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…However, few studies are available above the effect of DM on the activity of these Ca 2+clearing mechanisms VSMCs. In A7r5 cells, hyperglycemia was reported to induce a reduction in SERCA expression and activity (Searls et al, 2010;Tong et al, 2010) and an increase in PMCA and NCX activity (Han et al, 2022). However, our data showing that the decay phase of the initial increase in [Ca 2+ ] i evoked by ATP is accelerated in OZDF rat aortic VSMCs suggests that T2DM increases the activity of the Ca 2+ -clearing machinery.…”

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

confidence: 54%

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

confidence: 54%

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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“…The hyperpolarization of mitochondria in mouse vascular smooth muscle cells treated with HG was found to inhibit myosin light chain phosphatase, resulting in vascular smooth muscle contraction [ 24 ]. The exposure of murine aortic vascular smooth muscle cells to 30 mM glucose for 48 h was found to increase intracellular Ca 2+ levels through SOCE [ 25 ]. Because acute pancreatitis is frequently accompanied by ED [ 2 ] and hyperglycemia [ 26 ], intracellular Ca 2+ concentrations may be increased in the vascular smooth muscle cells of patients with acute pancreatitis, resulting in vascular hypercontraction.…”

Section: Discussionmentioning

confidence: 99%

“…Pretreatment with Rb 1 was found to inhibit Ca 2+ increase through SOCE in pulmonary arterial smooth muscle cells [ 20 ]. Moreover, Rb 1 significantly inhibited Ca 2+ influx through SOCE only in vascular smooth muscle cells, but not in vascular endothelial cells, exposed to 30 mM glucose for 48 h [ 25 ]. In agreement with these findings, the present study found that Rb 1 did not affect the agonist-induced vasoconstriction in aortas with HG and intact endothelium.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 Reduces Hyper-Vasoconstriction Induced by High Glucose and Endothelial Dysfunction in Rat Aorta

Park,

Shin,

Kim

et al. 2023

Pharmaceuticals

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Acute hyperglycemia induces oxidative damage and inflammation, leading to vascular dysfunction. Ginsenoside Rb1 (Rb1) is a major component of red ginseng with anti-diabetic, anti-oxidant and anti-inflammatory properties. Here, we investigated the beneficial effects and the underlying mechanisms of Rb1 on hypercontraction induced by high glucose (HG) and endothelial dysfunction (ED). The isometric tension of aortic rings was measured by myography. The rings were treated with NG-nitro-L-arginine methyl ester (L-NAME) to induce chemical destruction of the endothelium, and Rb1 was added after HG induction. The agonist-induced vasoconstriction was significantly higher in the aortic rings treated with L-NAME + HG50 than in those treated with HG50 or L-NAME (p = 0.011) alone. Rb1 significantly reduced the hypercontraction in the aortic rings treated with L-NAME + HG50 (p = 0.004). The ATP-sensitive K+ channel (KATP) blocker glibenclamide tended to increase the Rb1-associated reduction in the agonist-induced vasoconstriction in the rings treated with L-NAME + HG50. The effect of Rb1 in the aortic rings treated with L-NAME + HG50 resulted from a decrease in extracellular Ca2+ influx through the receptor-operated Ca2+ channel (ROCC, 10−6–10−4 M CaCl2, p < 0.001; 10−3–2.5 × 10−3 M CaCl2, p = 0.001) and the voltage-gated Ca2+ channel (VGCC, 10−6 M CaCl2, p = 0.003; 10−5–10−2 M CaCl2, p < 0.001), whereas Rb1 did not interfere with Ca2+ release from the sarcoplasmic reticulum. In conclusion, we found that Rb1 reduced hyper-vasoconstriction induced by HG and ED by inhibiting the ROCC and the VGCC, and possibly by activating the KATP in rat aorta. This study provides further evidence that Rb1 could be developed as a therapeutic target for ED in diabetes.

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Store-operated calcium entry: From physiology to tubular aggregate myopathy

Protasi

Girolami

Roccabianca

et al. 2023

Current Opinion in Pharmacology

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Ginsenoside Rg-1 prevents elevated cytosolic Ca2+ via store-operated Ca2+ entry in high-glucose–stimulated vascular endothelial and smooth muscle cells

Cited by 5 publications

References 43 publications

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

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

Ginsenoside Rb1 Reduces Hyper-Vasoconstriction Induced by High Glucose and Endothelial Dysfunction in Rat Aorta

Store-operated calcium entry: From physiology to tubular aggregate myopathy

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