ArticlePloS one2015
PKC and AKT Modulate cGMP/PKG Signaling Pathway on Platelet Aggregation in Experimental Sepsis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 19 citations in OpenAlex.
- Chrysoeriol Exerts Antiplatelet Effects by Regulating cAMP/cGMP and PI3K/MAPK Pathway.Biomolecules & therapeutics · 2026Article
- Pulmonary metabolic changes in a rabbit model of Pseudomonas aeruginosa pneumonia: insights from metabolomic analysis.BMC microbiology · 2025Article
- Structural insights into selective small molecule activation of PKG1α.Communications biology · 2023Article
- Article
- Inhibition of Phosphoinositide 3-Kinase Gamma Protects Endothelial Cells via the Akt Signaling Pathway in Sepsis-Induced Acute Kidney Injury.Kidney & blood pressure research · 2022Article
- Clotting Dysfunction in Sepsis: A Role for ROS and Potential for Therapeutic Intervention.Antioxidants (Basel, Switzerland) · 2021Review
- Haem oxygenase protects against thrombocytopaenia and malaria-associated lung injury.Malaria journal · 2020Article
- Article
- Cyclic nucleotide-dependent inhibitory signaling interweaves with activating pathways to determine platelet responses.Research and practice in thrombosis and haemostasis · 2018Review
- Predictive value of platelet aggregation rate in postpartum deep venous thrombosis and its possible mechanism.Experimental and therapeutic medicine · 2018Article
- The Potential Mechanism of Kushen Decoction in Treating Haemorrhoids: An Integration of Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation.IET systems biologyArticle
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sepsis severity has been positively correlated with platelet dysfunction, which may be due to elevations in nitric oxide (NO) and cGMP levels. Protein kinase C, Src kinases, PI3K and AKT modulate platelet activity in physiological conditions, but no studies evaluated the role of these enzymes in platelet aggregation in sepsis. In the present study we tested the hypothesis that in sepsis these enzymes positively modulate upstream the NO-cGMP pathway resulting in platelet inhibition. Rats were injected with lipopolysaccharide (LPS, 1 mg/kg, i.p.) and blood was collected after 6 h. Platelet aggregation was induced by ADP (10 μM). Western blotting assays were carried out to analyze c-Src and AKT activation in platelets. Intraplatelet cGMP levels were determined by enzyme immunoassay kit. Phosphorylation of c-SRC at Tyr416 was the same magnitude in platelets of control and LPS group. Incubation of the non-selective Src inhibitor PP2 (10 μM) had no effect on platelet aggregation of LPS-treated rats. LPS increased intraplatelet cGMP levels by 5-fold compared with control group, which was accompanied by 76% of reduction in ADP-induced platelet aggregation. The guanylyl cyclase inhibitor ODQ (25 μM) and the PKG inhibitor Rp-8-Br-PET-cGMPS (25 μM) fully reversed the inhibitory effect of LPS on platelet aggregation. Likewise, the PKC inhibitor GF109203X (10 μM) reversed the inhibition by LPS of platelet aggregation and decreased cGMP levels in platelets. AKT phosphorylation at Thr308 was significantly higher in platelets of LPS compared with control group, which was not reduced by PI3K inhibition. The AKT inhibitor API-1 (20 μM) significantly increased aggregation and reduced cGMP levels in platelets of LPS group. However, the PI3K inhibitor wortmannin and LY29004 had no effect on platelet aggregation of LPS-treated rats. Therefore, inhibition of ADP-induced platelet aggregation after LPS injection is mediated by cGMP/PKG-dependent mechanisms, and PKC and AKT act upstream upregulating this pathway.
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