Cell lines

Rabbit lens epithelial cells, N/N1003A cells

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

10-100 nM, 0-24 h,

Applications

In confluent rabbit lens epithelial cells (RLECs), okadaic acid (100 nM) within 3 to 24 h significantly induced cell apoptosis. Also, okadaic acid induced the expression of p53 and bax, which were necessary for the apoptotic programs. In N/N1003A cells, okadaic acid (10 nM) decreased total phosphatase activity by 20% and mainly inhibited PP-2A activity, while okadaic acid (100 nM) reduced 81% total phosphatase activity and inhibited PP-1 and PP-2A activity.

Animal models

Adult male Wistar rats

Dosage form

0-10 mg/kg, 30 min, injection cannula

Application

Intrastriatal infusion of okadaic acid (0.005, 0.05 and 0.5 nmol) increased CREB and Elk-1 phosphorylation and c-Fos immunoreactivity in the injected dorsal striatum in a dose-dependent manner. Okadaic acid (0.05 and 0.5 nM) increased c-fos mRNA expression in the dorsal striatum in a dose-dependent manner. Okadaic acid (0.05 and 0.5 nmol) at a survival time of 30 min significantly increased c-fos mRNA hybridization signals in the striatum in a dose-dependent manner. Okadaic acid at 0.05 nmol significantly increased pCREB and pElk-1. Okadaic acid (10 nM) inhibited PP-2A activity and okadaic acid (100 nM) inhibited both PP-2A and PP-1 activity.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

• Veterinary Research 52.1 (2021): 1-16. PMID:34930429

Okadaic acid is a marine sponge toxin which potently inhibits certain serine/threonine protein phosphatases. This cell permeable inhibitor targets the multiple isoforms of PP1 (IC50 = 10-50 nM), both isoforms of PP2A (IC50 = 0.5 nM) and PP3 (IC50 = 4 nM).[1],[2],[3] It is a very weak inhibitor of PP2B (IC50 > 2 μM) and does not inhibit PP2C or other phosphatases.[1],[3 ]Presumably through these actions, okadaic acid is a potent carcinogen and induces tau phosphorylation.[4],[5] In sponge, okadaic acid plays a role in defense, inducing apoptosis in symbiotic or parasitic annelids.[6]

Reference:
[1]. Bialojan, C., and Takai, A. Inhibitory effect of a marine-sponge toxin, okadaic acid, on protein phosphatases. Specificity and kinetics. Biochemistry Journal 256, 283-290 (1988).
[2]. Gupta, V., Ogawa, A.K., Du, X., et al. A model for binding of structurally diverse natural product inhibitors of protein phosphatases PP1 and PP2A. Journal of Medicinal Chemistry 40, 3199-3206 (1997).
[3]. McCluskey, A., Sim, A.T.R., and Sakoff, J.A. Serine-threonine protein phosphatase inhibitors: Development of potential therapeutic strategies. Journal of Medicinal Chemistry 45(6), 1151-1175 (2002).
[4]. Suganuma, M., Fujiki, H., Suguri, H., et al. Okadaic acid: An additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proceedings of the National Academy of Sciences of the United States of America 85, 1768-1771 (1988).
[5]. Zhang, Z., and Simpkins, J.W. Okadaic acid induces tau phosphorylation in SH-SY5Y cells in an estrogen-preventable manner. Brain Research 1345, 176-181 (2010).
[6]. Schroder, H.C., Breter, H.J., Fattorusso, E., et al. Okadaic acid, an apoptogenic toxin for symbiotic/parasitic annelids in the demosponge Suberites domuncula. Applied and Environmental Microbiology 72(7), 4907-4916 (2006).