| Title | Alpha-Actinin-4 is a Possible Target Protein for Aristolochic Acid I in Human Kidney Cells In Vitro |
| Authors | Wang, Dan Li, Xiao-Wei Wang, Xuan Tan, Huan-Ran Jia, Yan Yang, Li Li, Xiao-Mei Shang, Ming-Ying Xu, Feng Yang, Xing-Xin Shoyama, Yukihiro Cai, Shao-Qing |
| Affiliation | Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, 38 Xue Yuan Rd, Beijing 100191, Peoples R China. Peking Univ, Dept Biol Chem, Sch Pharmaceut Sci, 38 Xue Yuan Rd, Beijing 100191, Peoples R China. Peking Univ, Dept Pharmacol, Hlth Sci Ctr, Beijing 100191, Peoples R China. Peking Univ, Div Renal, Dept Med, Hosp 1, Beijing 100034, Peoples R China. Nagasaki Int Univ, Dept Pharmacognosy, Fac Pharmaceut Sci, Nagasaki 8593298, Japan. Peking Univ, State Key Lab Nat & Biomimet Drugs, Sch Pharmaceut Sci, 38 Xue Yuan Rd, Beijing 100191, Peoples R China. Wang, X (reprint author), Peking Univ, Dept Biol Chem, Sch Pharmaceut Sci, 38 Xue Yuan Rd, Beijing 100191, Peoples R China. |
| Keywords | alpha-Actinin-4 Aristolochic Acid Monoclonal Antibody Immunocytochemistry Immunoprecipitation (IP) HK-2 Cells IP-MS/MS INTERSTITIAL FIBROSIS NEPHROPATHY RATS APOPTOSIS CANCER TRANSPORT ARTHRITIS TOXICITY CAPTURE |
| Issue Date | 2016 |
| Publisher | AMERICAN JOURNAL OF CHINESE MEDICINE |
| Citation | AMERICAN JOURNAL OF CHINESE MEDICINE.2016,44,(2),291-304. |
| Abstract | Aristolochic acid I (AA-I) is a strong nephrotoxin, carcinogen, and mutagen found in plants such as the Aristolochia species. The mechanisms underlying AA-I toxicity in the kidneys are poorly understood. In this study, we aimed to gain insight into the mechanism of AA-I nephrotoxicity by analyzing the uptake, subcellular distribution, and intracellular targets of AA-I in the human kidney cell line HK-2 using immunocytochemistry, immunoprecipitation, and LC-MS/MS. In HK-2 cells incubated with 20 mu g/mL AA-I for different periods of time (up to 12 h), AA-I was detected by a specific monoclonal antibody (MAb) against AA-I, both in the cytoplasm and nuclei. Nuclear localization depended on the exposure time. A protein with the molecular weight of 100 kDa was immunoprecipitated with the anti-AA-I MAb from the AA-I-treated cell lysates and was identified by LC-MS/MS as alpha-actinin-4 after digestion of the protein, and was confirmed by immunoblotting with a specific anti-alpha-actinin-4 MAb. This evidence shows, for the first time, that alpha-actinin-4 is a protein targeted by AA-I in kidney cells. Our findings strongly suggest an association between alpha-actinin-4 and AA-I nephrotoxic activity. |
| URI | http://hdl.handle.net/20.500.11897/434113 |
| ISSN | 0192-415X |
| DOI | 10.1142/S0192415X16500178 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 药学院 第一医院 天然药物与仿生药物国家重点实验室 |
