Aldehyde dehydrogenase induction in arsenic-exposed rat bladder epithelium.
Arsenic is widely distributed in the environment. Many human cancers, including urothelial carcinoma (UC), show a dose-dependent relationship with arsenic exposure in the south-west coast of Taiwan (also known as the blackfoot disease (BFD) areas). However, the molecular mechanisms of arsenic-mediated UC carcinogenesis has not yet been defined. In vivo study, the rat bladder epithelium were exposed with arsenic for 48 h. The proteins were extracted from untreated and arsenic-treated rat bladder cells and utilized two-dimensional gel electrophoresis and mass spectrometry. Selected peptides were extracted from the gel and identified by quadrupole-time of flight (Q-TOF) Ultima-Micromass spectra. The significantly difference expression of proteins in arsenic-treated groups as compared with untreated groups was confirmed by immunohistochemistry (IHC) and western blotting. We found that thirteen proteins were down-regulated and nine proteins were up-regulated in arsenic-treated rat bladder cells when compared with untreated groups. The IHC and western blotting results confirmed that aldehyde dehydrogenase (ALDH) protein was up-regulated in arsenic-treated rat bladder epithelium. Expression of ALDH protein was significantly higher in UC patients from BFD areas than those from non-BFD areas using IHC (p=0.018). In conclusion, the ALDH protein expression could be used as molecular markers for arsenic-induced transformation.
Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Ya-Chun
YC
Huang
Department of Dermatology, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.
Hsin-Su
HS
Yu
Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan; Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung City, Taiwan. Electronic address: cychai@kmu.edu.tw.
Chee-Yin
CY
Chai
D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis*; D000818:Animals; D020261:Arsenic Poisoning / Q000150:complications*; D018053:Arsenites / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced* / Q000201:enzymology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation; D001743:Urinary Bladder / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced* / Q000201:enzymology
D018053:Arsenites; D015415:Biomarkers; D000444:Aldehyde Dehydrogenase
Arsenic; Molecular biomarkers; Oncoproteins; Rat bladder epithelium; Urothelial carcinoma