Surgical Indications in Hypophosphataemic Rickets

Bueno-Sánchez, Ana M

doi:10.1007/s12325-019-01179-y

Cited by 3 publications

(1 citation statement)

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“…Platelet apoptosis and activation can occur separately downstream of Akt. It has been shown previously that calpain activation mediated by Ca 2+ mobilization is essential for Akt-dependent platelet activation signaling ( Chen et al, 2004 ; Bueno-Sánchez, 2020 ). In order to confirm the ability of CBZ in calpain inhibition, we found that CBZ markedly reduced A23187 mediated calpain activation.…”

Section: Discussionmentioning

confidence: 99%

Carbamazepine Induces Platelet Apoptosis and Thrombocytopenia Through Protein Kinase A

et al. 2021

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Carbamazepine is extensively used worldwide to treat a wide range of disorders such as epilepsy, peripheral neuralgia and bipolar disorder. Thrombocytopenia and hemorrhage have been identified in multiple carbamazepine-treated patients. However, the underlying mechanism remains poorly understood. Here, we show that platelets undergo apoptosis after carbamazepine treatment. The apoptotic platelets induced by carbamazepine are rapidly removed in vivo, which accounts for thrombocytopenia. We found that carbamazepine treatment attenuates the phosphorylation level of bcl-xl/bcl-2-associated death promoter (BAD), vasodilator-associated stimulated phosphoprotein (VASP) and GPIbβ in platelets, indicating an inhibition effect on protein kinase A (PKA). We further demonstrated that carbamazepine reduced PKA activity through PI3K/Akt/PDE3A signaling pathway. Pharmacological activation of PKA or inhibition of PI3K/Akt/PDE3A protects platelets from apoptosis induced by carbamazepine. Importantly, PDE3A inhibitors or PKA activator ameliorates carbamazepine-mediated thrombocytopenia in vivo. These findings shed light on a possible mechanism of carbamazepine-induced thrombocytopenia, designating PDE3A/PKA as a potential therapeutic target in the treatment of carbamazepine-induced thrombocytopenia.

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Section: Discussionmentioning

confidence: 99%