Objective: Members of the protein kinase C (PKC) family are shown to positively and negatively regulate platelet activation. Although positive regulatory roles are extensively studied, negative regulatory roles of PKCs are poorly understood. We investigated the mechanism and specific isoforms involved in PKC-mediated negative regulation of ADP-induced functional responses.
Methods And Results: A pan-PKC inhibitor, GF109203X, potentiated ADP-induced cPLA(2) phosphorylation and thromboxane generation as well as ERK activation and intracellular calcium (Ca(2+)(i)) mobilization, 2 signaling molecules, upstream of cPLA(2) activation. Thus, PKCs inhibit cPLA(2) activation by inhibiting ERK and Ca(2+)(i) mobilization. Because the inhibitor of classic PKC isoforms, GO-6976, did not affect ADP-mediated thromboxane generation, we investigated the role of novel class of PKC isoforms. ADP-induced thromboxane generation, calcium mobilization, and ERK phosphorylation were potentiated in PKCε null murine platelets compared with platelets from wild-type littermates. Interestingly, when thromboxane release is blocked, ADP-induced aggregation in PKCε knockout and wild-type was similar, suggesting that PKCε does not affect ADP-induced aggregation directly. PKCε knockout mice exhibited shorter times to occlusion in an FeCl(3)-induced arterial injury model and shorter bleeding times in tail-bleeding experiments.
Conclusions: We conclude that PKCε negatively regulates ADP-induced thromboxane generation in platelets and offers protection against thrombosis.
Ketoprofen is a non-steroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation in dogs. Despite having effective analgesic efficacy, prolonged oral administration has been associated with adverse effects. Transdermal delivery of ketoprofen has reduced the incidence of adverse effects in humans and could potentially be used in veterinary clinical medicine.
This study aims to reveal the effect and mechanism of Dendrobii Officinalis Caulis water extract on the rat model of hyperviscosity induced by a high-sugar, high-salt, and high-fat diet. Thirty-six male SD rats were randomized into normal, model, Compound Danshen Tablets(0.5 g·kg~(-1)), and low-, medium-, and high-dose(0.
This study tested the hypothesis that coronary artery adaptations during the postpartum period are related to underlying reductions in endothelium-dependent relaxation and/or augmented smooth muscle vasoconstrictor responsiveness. In vivo experiments were performed in control (nonpregnant) and postpartum swine 35-45 days post-delivery, with isometric tension experiments performed in isolated coronary arteries from those animals. Coronary artery rings demonstrated increases in active tension generation following incremental increases in passive stretch with no differences between groups.
Understanding platelet protein functions improves diagnosis and treatment of platelet disorders.
Researchers used human Disabled-2 knock-in (hDAB2-KI) mice to study how hDab2 regulates platelet function and bleeding in cases of low platelet counts (thrombocytopenia).
Findings show that hDab2 enhances certain platelet responses, leading to reduced bleeding time and indicating its significant role in managing bleeding severity related to thrombocytopenia.
Myo-inositol plays a key role in the vasculature and may be beneficial for preventing harmful environmental effects. In this study aortic rings were isolated from middle-aged (12-month-old) male Wistar rats and preincubated with myo-inositol (0.01-100 mg/L) for 2 h.
