title: Identification of nuclear phosphoproteins as novel tobacco markers in mouse lung tissue following short-term exposure to tobacco smoke.
abstract: Smoking is a risk factor for lung diseases, including chronic obstructive pulmonary disease and lung cancer. However, the molecular mechanisms mediating the progression of these diseases remain unclear. Therefore, we sought to identify signaling pathways activated by tobacco-smoke exposure, by analyzing nuclear phosphoprotein expression using phosphoproteomic analysis of lung tissue from mice exposed to tobacco smoke. Sixteen mice were exposed to tobacco smoke for 1 or 7 days, and the expression of phosphorylated peptides was analyzed by mass spectrometry. A total of 253 phosphoproteins were identified, including FACT complex subunit SPT16 in the 1-day exposure group, keratin type 1 cytoskeletal 18 (K18), and adipocyte fatty acid-binding protein, in the 7-day exposure group, and peroxiredoxin-1 (OSF3) and spectrin β chain brain 1 (SPTBN1), in both groups. Semi-quantitative analysis of the identified phosphoproteins revealed that 33 proteins were significantly differentially expressed between the control and exposed groups. The identified phosphoproteins were classified according to their biological functions. We found that the identified proteins were related to inflammation, regeneration, repair, proliferation, differentiation, morphogenesis, and response to stress and nicotine. In conclusion, we identified proteins, including OSF3 and SPTBN1, as candidate tobacco smoke-exposure markers; our results provide insights into the mechanisms of tobacco smoke-induced diseases.
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Niimori-Kita
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ogino
authors.affiliation: AMR Incorporated, 2-13-18, Nakane, Meguro-ku, Tokyo 152-0031, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Mikami
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Daikai
authors.initials: D
authors.lastname: Koizumi
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kudoh
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Nakamura
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Misumi
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Tadasuke
authors.initials: T
authors.lastname: Shimomura
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: AMR Incorporated, 2-13-18, Nakane, Meguro-ku, Tokyo 152-0031, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Usui
authors.affiliation: Isotope Research Center, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Nagahara
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-8556, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
keywords: 60s-RP, 60s ribosomal protein L10E; AFABP, adipocyte fatty acid-binding protein; ALDH2, aldehyde dehydrogenase, mitochondrial; COPD, chronic obstructive pulmonary disorder; CRP1, cysteine and glycine-rich protein 1; ERK(1/2), extracellular signal regulated kinase 1/2; FACTp140, FACT complex subunit SPT16; HIP1, Huntingtin-interacting protein 1; IL, interleukin; JNK, c-Jun NH2-terminal kinase; Jak2, tyrosine-protein kinase JAK2; K18, keratin type 1 cytoskeletal 18; K8, keratin type 2 cytoskeletal 8; LIM, LIM/homeobox protein; MAPK3, mitogen-activated protein kinase 3; NF-κB, nuclear factor-kappa B; Nuclear phosphoprotein; OSF3, peroxiredoxin-1; PKC-α, protein kinase C-α; PRP19, pre-mRNA-processing factor 19; Phosphoproteomic analysis; ROS, reactive oxygen species; SPTBN1, spectrin β chain brain 1; STAT, signal transducer and activator of transcription; Signaling pathways; TGF-β, Transforming growth factor-β; TIM, mitochondrial import inner membrane translocase subunit Tim9; TNF, tumor necrosis factor; TNFR2, tumor necrosis factor receptor 2; TRAP1, heat shock protein 75 kDa; Tobacco smoke exposure; p100, serine protease P100; pSTAT3-Tyr705, phosphorylated STAT3