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Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity.
Eur J Pharmacol. 2012 Feb 15; 676(1-3):57-63.EJ

Abstract

In the treatment of Parkinson's disease, potent disease-modifying drugs are still needed to halt progressive dopaminergic neurodegeneration. We have previously shown that meloxicam, an oxicam non-steroidal anti-inflammatory drug (NSAID), elicits a potent neuroprotective effect against 1-methyl-4-phenyl pyridinium (MPP(+))-induced toxicity in human dopaminergic SH-SY5Y neuroblastoma cells. This cyclooxygenase-independent neuroprotection of meloxicam is mediated via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; however, the specific chemical structure involved in inducing neuroprotection remains unresolved. In this study, we therefore investigated the structure-specific for eliciting the neuroprotective effect by examining a series of NSAIDs against MPP(+) toxicity in SH-SY5Y cells. Three oxicam-bearing NSAIDs showed potent neuroprotective effects, although none of the other 10 oxicam-nonbearing NSAIDs (3 salicylates, 6 coxibs and 1 polyphenol) or 3 piroxicam analogs (including ampiroxicam, a precursor of piroxicam) exerted any neuroprotection. Tenoxicam and piroxicam prevented MPP(+)-induced reduction of phosphorylated Akt levels in cells: a protective mechanism similar to that of meloxicam. Therefore, the oxicam structure was likely to be responsible for exhibiting the neuroprotection by sustaining survival-signaling in dopaminergic cells. The present results raise the possibility that the oxicam-bearing NSAIDs may serve as potential therapeutic drugs to retard or terminate progression of Parkinson's disease via a novel mechanism.

Authors+Show Affiliations

Department of Hospital Pharmacy & Pharmacology, Asahikawa Medical University, Asahikawa 078-8510, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22182582

Citation

Tasaki, Yoshikazu, et al. "Oxicam Structure in Non-steroidal Anti-inflammatory Drugs Is Essential to Exhibit Akt-mediated Neuroprotection Against 1-methyl-4-phenyl Pyridinium-induced Cytotoxicity." European Journal of Pharmacology, vol. 676, no. 1-3, 2012, pp. 57-63.
Tasaki Y, Yamamoto J, Omura T, et al. Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity. Eur J Pharmacol. 2012;676(1-3):57-63.
Tasaki, Y., Yamamoto, J., Omura, T., Noda, T., Kamiyama, N., Yoshida, K., Satomi, M., Sakaguchi, T., Asari, M., Ohkubo, T., Shimizu, K., & Matsubara, K. (2012). Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity. European Journal of Pharmacology, 676(1-3), 57-63. https://doi.org/10.1016/j.ejphar.2011.11.046
Tasaki Y, et al. Oxicam Structure in Non-steroidal Anti-inflammatory Drugs Is Essential to Exhibit Akt-mediated Neuroprotection Against 1-methyl-4-phenyl Pyridinium-induced Cytotoxicity. Eur J Pharmacol. 2012 Feb 15;676(1-3):57-63. PubMed PMID: 22182582.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity. AU - Tasaki,Yoshikazu, AU - Yamamoto,Joe, AU - Omura,Tomohiro, AU - Noda,Toshihiro, AU - Kamiyama,Naoya, AU - Yoshida,Koichi, AU - Satomi,Machiko, AU - Sakaguchi,Tomoki, AU - Asari,Masaru, AU - Ohkubo,Tomoko, AU - Shimizu,Keiko, AU - Matsubara,Kazuo, Y1 - 2011/12/07/ PY - 2011/07/12/received PY - 2011/11/22/revised PY - 2011/11/27/accepted PY - 2011/12/21/entrez PY - 2011/12/21/pubmed PY - 2012/5/19/medline SP - 57 EP - 63 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 676 IS - 1-3 N2 - In the treatment of Parkinson's disease, potent disease-modifying drugs are still needed to halt progressive dopaminergic neurodegeneration. We have previously shown that meloxicam, an oxicam non-steroidal anti-inflammatory drug (NSAID), elicits a potent neuroprotective effect against 1-methyl-4-phenyl pyridinium (MPP(+))-induced toxicity in human dopaminergic SH-SY5Y neuroblastoma cells. This cyclooxygenase-independent neuroprotection of meloxicam is mediated via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway; however, the specific chemical structure involved in inducing neuroprotection remains unresolved. In this study, we therefore investigated the structure-specific for eliciting the neuroprotective effect by examining a series of NSAIDs against MPP(+) toxicity in SH-SY5Y cells. Three oxicam-bearing NSAIDs showed potent neuroprotective effects, although none of the other 10 oxicam-nonbearing NSAIDs (3 salicylates, 6 coxibs and 1 polyphenol) or 3 piroxicam analogs (including ampiroxicam, a precursor of piroxicam) exerted any neuroprotection. Tenoxicam and piroxicam prevented MPP(+)-induced reduction of phosphorylated Akt levels in cells: a protective mechanism similar to that of meloxicam. Therefore, the oxicam structure was likely to be responsible for exhibiting the neuroprotection by sustaining survival-signaling in dopaminergic cells. The present results raise the possibility that the oxicam-bearing NSAIDs may serve as potential therapeutic drugs to retard or terminate progression of Parkinson's disease via a novel mechanism. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/22182582/Oxicam_structure_in_non_steroidal_anti_inflammatory_drugs_is_essential_to_exhibit_Akt_mediated_neuroprotection_against_1_methyl_4_phenyl_pyridinium_induced_cytotoxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(11)01513-5 DB - PRIME DP - Unbound Medicine ER -