title: Tigecycline prevents LPS-induced release of pro-inflammatory and apoptotic mediators in neuronal cells.
abstract: Pro-inflammatory and pro-apoptotic mediators have been involved in the pathogenesis of neurodegenerative diseases. Tigecycline (Tig), a glycylcycline antibiotic and an analog of Minocycline, is shown to exert anti-inflammatory effects that are distinct from its anti-microbial activity. Its neuroprotective mechanism is unknown. In this study, we investigated the direct protective mechanisms of tigecycline against lipopolysaccharide (LPS)-induced Rat pheochromocytoma (PC12) cells. The results showed that tigecycline significantly attenuated the expression and the release of nuclear factor-kappa beta (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), as well as nitric oxide (NO) levels in LPS-induced PC12 cells. In addition, tigecycline dose-dependently decreased cytochrome c release and caspase-3 activity. This later finding corroborated the results of decreased pro-apoptotic Bad, and increased anti-apoptotic Bcl-2 protein expression thus, confirming a neuroprotective effect of the drug in differentiated PC12 cells induced with LPS. The findings of our study suggest new targets for tigecycline and support the potential for tigecycline to be investigated as a therapeutic agent for neurodegenerative disorders.
authors.affiliation: Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy & Health Sciences, Long Island University, Brooklyn, NY 11201, USA.
authors.forename: Radhi M
authors.initials: RM
authors.lastname: Yagnik
authors.forename: Kenza E
authors.initials: KE
authors.lastname: Benzeroual
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D000078304:Tigecycline; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D000078304:Tigecycline; D045304:Cytochromes c; D053148:Caspase 3; D008911:Minocycline