Anti‑platelet activity of mineral‑balanced deep sea water is mediated via the regulation of Akt and ERK pathway crosstalk

Nam,Gi   Suk; Lee,Kyu‑Shik; Nam,Kyung‑Soo

doi:10.3892/ijmm.2019.4424

Anti‑platelet activity of mineral‑balanced deep sea water is mediated via the regulation of Akt and ERK pathway crosstalk

Authors:
- Gi Suk Nam
- Kyu‑Shik Lee
- Kyung‑Soo Nam
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Affiliations: Department of Pharmacology and Intractable Disease Research Center, School of Medicine, Dongguk University, Gyeongju, Gyeongsangbuk‑do 38066, Republic of Korea
Published online on: December 10, 2019 https://doi.org/10.3892/ijmm.2019.4424
Pages: 658-668

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Abstract

Mineral‑balanced deep sea water (MBDSW), an unlimited natural sea source, has been demonstrated to minimize the risk of developing cardiovascular diseases, such as obesity, hypertension, inflammation and hyperlipidemia. This study investigated the effects of MBDSW [magnesium (Mg):calcium (Ca) ratio, 3:1] on platelet activation. MBDSW significantly inhibited the collagen‑ and thrombin‑induced platelet aggregation of human platelets. In collagen‑induced platelets, MBDSW inhibited intracellular calcium mobilization, granule secretion [serotonin, adenosine triphosphate (ATP) and P‑selectin expression] and thromboxane A2 (TXA2) production. Moreover, MBDSW markedly inhibited Akt and extracellular signal‑regulated kinase (ERK) phosphorylation, but not that of c‑Jun N‑terminal kinase (JNK) and p38. Moreover, MBDSW phosphorylated inositol 1,4,5‑triphosphate receptor (IP3R) and vasodilator‑stimulated phosphoprotein (VASP), and it increased the cyclic adenosine monophosphate (cAMP) level in collagen‑induced human platelets. Dipyridamole, a phosphodiesterase (PDE) inhibitor, significantly increased the cAMP level and regulated the Akt, ERK and VASP (Ser157) levels in a manner similar to that of MBDSW. In addition, LY294002, an Akt inhibitor, inhibited the phosphorylation of ERK, and U0126, an ERK inhibitor, inhibited the phosphorylation of Akt. Taken together, the results of the present investigation suggest that the inhibitory effects of MBDSW on platelet aggregation may be associated with the cross‑inhibition of Akt and ERK phosphorylation. These results strongly indicate that MBDSW may have preventive or therapeutic potential for platelet aggregation‑mediated diseases, such as thrombosis, atherosclerosis and myocardial infarction.

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