Inflammation-induced protein carbonylation contributes to poor prognosis for cholangiocarcinoma

详细信息	查看全文 | 推荐本文 |

• 作者：Raynoo Thanan^a ; ^b ; ^c ; ¹ ; Shinji Oikawa^a ; Puangrat Yongvanit^b ; ^d ; Yusuke Hiraku^a ; Ning Ma^e ; Somchai Pinlaor^d ; ^f ; Chawalit Pairojkul^d ; ^g ; Chaisiri Wongkham^b ; ^d ; Banchob Sripa^d ; ^g ; Narong Khuntikeo^d ; ^h ; Shosuke Kawanishiⁱ ; ^{kawanisi@suzuka-u.ac.jp} ; Mariko Murata^a ; ^{mmurata@doc.medic.mie-u.ac.jp}
• 关键词：CCA ; cholangiocarcinoma ; LC&ndash ; MALDI ; liquid chromatography&ndash ; matrix-assisted laser desorption/ionization ; TOF ; time-of-flight ; MS ; mass spectrometry ; CBB ; Coomassie brilliant blue ; HSP70.1 ; heat shock protein 70-kDa protein 1 ; A1AT ; 伪1-antitrypsi
• 刊名：Free Radical Biology and Medicine
• 出版年：2012
• 期刊代码：105_08915849
• 类别：med
• 出版时间：15 April, 2012
• 卷：52
• 期：8
• 页码：1465-1472
• 文件大小：1284 K

摘要

Carbonylation is an irreversible and irreparable protein modification induced by oxidative stress. Cholangiocarcinoma (CCA) is associated with chronic inflammation caused by liver fluke infection. To investigate the relationship between protein carbonylation and CCA progression, carbonylated proteins were detected by 2D OxyBlot and identified by MALDI-TOF/TOF analyses in pooled CCA tissues in comparison to adjacent nontumor tissues and normal liver tissues. We identified 14 highly carbonylated proteins in CCA tissues. Immunoprecipitation and Western blot analyses of individual samples confirmed significantly greater carbonylation of serotransferrin, heat shock protein 70-kDa protein 1 (HSP70.1), and 伪1-antitrypsin (A1AT) in tumor tissues compared to normal tissues. The oxidative modification of these proteins was significantly associated with poor prognoses as determined by the Kaplan-Meier method. LC-MALDI-TOF/TOF mass spectrometry identified R50, K327, and P357 as carbonylated sites in serotransferrin, HSP70.1, and A1AT, respectively. Moreover, iron accumulation was significantly higher in CCA tissues with, compared to those without, carbonylated serotransferrin. We conclude that carbonylated serotransferrin-associated iron accumulation may induce oxidative stress via the Fenton reaction, and the carbonylation of HSP70.1 with antioxidative property and A1AT with protease inhibitory capacity may cause them to become dysfunctional, leading to CCA progression.