Biomedical subjects

Ji-Yoon Noh

Publications and source records attributed to Ji-Yoon Noh.

4 recordsLinked to original sources

PubMed2007

Lead-induced procoagulant activation of erythrocytes through phosphatidylserine exposure may lead to thrombotic diseases.

Lead (Pb) is a ubiquitous heavy metal pollutant in various environmental media, especially in food and drinking water. In human blood, about 95% of lead is associated with erythrocytes, suggesting that erythrocytes could be an important target of lead toxicity in the cardiovascular system. Recent studies suggested that erythrocytes could contribute to blood coagulation via phosphatidylserine (PS) exposure and resultant procoagulant activation. We investigated the effects of lead on the procoagulant activity of erythrocytes using in vitro human erythrocyte and in vivo rat models. In a flow cytometric analysis, lead (Pb2+) enhanced PS exposure on human erythrocytes in a concentration- and time-dependent manner. The concentration of lead (1-5 microM) used in the current investigation is well within the ranges observed in blood from lead-exposed populations. PS exposure by lead appeared to be mediated by increased intracellular calcium levels as shown by 19F-NMR and intracellular ATP depletion. Consistent with these findings, the activity of scramblase, which is important in the induction of PS exposure, was enhanced, whereas the activity of flippase, which translocates exposed PS to inner membrane, was inhibited by lead treatment. Furthermore, lead-exposed erythrocytes increased thrombin generation as determined by a prothrombinase assay and accelerated the coagulation process initiated by tissue factor in plasma. These procoagulant activations by lead were also confirmed in vivo. Administration of lead significantly enhanced PS exposure on erythrocytes and, more importantly, elevated thrombus formation in a rat venous thrombosis model. These results suggest that lead exposure can provoke procoagulant activity in erythrocytes by PS exposure, contributing to enhanced clot formation. These data will provide new insights into the mechanism of lead-induced cardiovascular diseases.

Adolescent↗

PubMed2006

Lysophosphatidic acid induces thrombogenic activity through phosphatidylserine exposure and procoagulant microvesicle generation in human erythrocytes.

OBJECTIVE: Although erythrocytes have been suggested to play a role in blood clotting, mediated through phosphatidylserine (PS) exposure and/or PS-bearing microvesicle generation, an endogenous substance that triggers the membrane alterations leading to a procoagulant activity in erythrocytes has not been reported. We now demonstrated that lysophosphatidic acid (LPA), an important lipid mediator in various pathophysiological processes, induces PS exposure and procoagulant microvesicle generation in erythrocytes, which represent a biological significance resulting in induction of thrombogenic activity. METHODS AND RESULTS: In human erythrocytes, LPA treatment resulted in PS exposure on remnant cells and PS-bearing microvesicle generation in a concentration-dependent manner. Consistent with the microvesicle generation, scanning electron microscopic study revealed that LPA treatment induced surface changes, alteration of normal discocytic shape into echinocytes followed by spherocytes. Surprisingly, chelation of intracellular calcium did not affect LPA-induced PS exposure and microvesicle generation. On the other hand, protein kinase C (PKC) inhibitors significantly reduced PS exposure and microvesicle generation induced by LPA, reflecting the role of calcium-independent PKC. Activation of PKC was confirmed by Western blot analysis showing translocation of calcium-independent isoform, PKCzeta, to erythrocyte membrane. The activity of flippase, which is important in the maintenance of membrane asymmetry, was also inhibited by LPA. Furthermore, LPA-exposed erythrocytes actually potentiated the thrombin generation as determined by prothrombinase assay and accelerated the coagulation process initiated by recombinant human tissue factor in plasma. The adherence of erythrocytes to endothelial cells, another important feature of thrombogenic process, was also stimulated by LPA treatment. CONCLUSIONS: These results suggested that LPA-exposed erythrocytes could make an important contribution to thrombosis mediated through PS exposure and procoagulant microvesicle generation.

Adolescent↗

PubMed2006

Antiplatelet and antithrombotic activities of Korean Red Ginseng.

The antiplatelet and antithrombotic activities of Korean Red Ginseng (KRG) were examined on rat carotid artery thrombosis in vivo, and platelet aggregation in vitro and ex vivo. Administration of KRG to rats not only prevented carotid artery thrombosis in vivo in a dose-dependent manner, but also significantly inhibited ADP- and collagen-induced platelet aggregation ex vivo, while failed to prolong coagulation times such as activated partial thromboplastin time (APTT) and prothrombin time (PT), indicating the antithrombotic effect of KRG might be due to its antiplatelet aggregation rather than anticoagulation effect. In line with the above observations, KRG inhibited U46619-, arachidonic acid-, collagen- and thrombin-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with IC50 values of 620 +/- 12, 823 +/- 22, 722 + 21 and 650 +/- 14 microg/mL, respectively. Accordingly, KRG also inhibited various agonists-induced platelet serotonin secretions as it suppressed platelet aggregation. These results suggest that KRG has a potent antithrombotic effect in vivo, which may be due to antiplatelet rather than anticoagulation activity, and KRG intake may be beneficial to the individuals with high risks of thrombotic and cardiovascular diseases.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2006

Shear stress-induced pH increase in plasma is mediated by a decrease in P(CO(2)): the increase in pH enhances shear stress-induced P-selectin expression in platelets.

To investigate shear stress-induced platelet activation, the cone-plate viscometer or the Couette rotational viscometer has been widely used. In a previous report, it was shown that shearing platelet-rich plasma using a Couette rotational viscometer could lead to an increase in pH by CO(2) release. However, any clear mechanism has not been provided. In this study, we examined whether shearing cell free plasma only using a cone-plate viscometer can also induce pH increase and studied the underlying mechanism of shear-induced pH increase by directly measuring total CO(2) (T(CO(2))) and CO(2) tension (P(CO(2))). When human plasma was sheared using a cone-plate viscometer, the pH of the human plasma increased time- and shear rate-dependently. Although T(CO(2)) of human plasma was not affected, P(CO(2)) was decreased by shearing, indicating that the decreased P(CO(2)) is associated with a pH increase of plasma. In addition, the pH of bicarbonate-containing suspension buffer was also shown to be increased by shearing; suggesting that the platelet studies using suspension buffers containing bicarbonate could be affected similarly. The effects of pH changes on shear stress-induced platelet activation were also investigated in the same in vitro systems. While shear stress-induced platelet aggregation was not affected by the pH changes, P-selectin expression was significantly increased in accordance with the pH increase. In conclusion, shear stress using a cone-plate viscometer induces pH increase in plasma or bicarbonate-containing suspension buffer through a P(CO(2)) decrease and the pH changes alone can contribute to platelet activation by enhancing shear stress-induced P-selectin expression.

Analysis of Variance↗