title: Pneumolysin induces cellular senescence by increasing ROS production and activation of MAPK/NF-κB signal pathway in glial cells.
abstract: Senescence is an irreversible proliferation arrest that is induced by various stress stimuli including genotoxin. Pneumolysin (PLY) is a pathogenicity factor unique to Streptococcus pneumoniae that is important in pneumococcal-induced diseases such as otitis media, meningitis and pneumonia. However, the cell fate response to the toxin is mechanistically unclear. We investigated the effect of PLY on cellular senescence in BV-2 microglial cells. Exposure to PLY resulted in changes in the expression of phospho-p53, p21, p16, pRb and CDK2 and increased the number of senescence associated β-gal positive cells. PLY-treatment also increased PAI-1 expression and cell proliferation arrest in concentration- and time-dependent manners. PLY induced NF-κB activation and phosphorylation of SIRT-1, ERK1/2, JNK, and p38 MAPK. In addition, PLY increased the production of reactive oxygen species. Overall, the results suggest that PLY regulates microglial cellular senescence by enhancing production of reactive oxygen species, activation of MAPK and NF-κB, and phosphorylation of SIRT-1.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyunggi-do, 16419, Republic of Korea.
authors.forename: Ii-Seul
authors.initials: IS
authors.lastname: Kwon
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyunggi-do, 16419, Republic of Korea.
authors.forename: Jinwook
authors.initials: J
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyunggi-do, 16419, Republic of Korea.
authors.forename: Dong-Kwon
authors.initials: DK
authors.lastname: Rhee
authors.affiliation: School of Food Sciences & Biotechnology, College of Agriculture & Life Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.
authors.forename: Byung-Oh
authors.initials: BO
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyunggi-do, 16419, Republic of Korea. Electronic address: snpyo@skku.edu.
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae; D013301:Streptolysins / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D020928:Mitogen-Activated Protein Kinases; D056564:Sirtuin 1
keywords: Cellular senescence; Glial cells; MAPK; NF-κB; Pneumolysin; ROS