title: A SILAC-Based Approach Elicits the Proteomic Responses to Vancomycin-Associated Nephrotoxicity in Human Proximal Tubule Epithelial HK-2 Cells.
abstract: Vancomycin, a widely used antibiotic, often induces nephrotoxicity, however, the molecular targets and underlying mechanisms of this side effect remain unclear. The present study aimed to examine molecular interactome and analyze the signaling pathways related to the vancomycin-induced nephrotoxicity in human proximal tubule epithelial HK-2 cells using the stable isotope labeling by amino acids in cell culture (SILAC) approach. The quantitative proteomic study revealed that there were at least 492 proteins interacting with vancomycin and there were 290 signaling pathways and cellular functions potentially regulated by vancomycin in HK-2 cells. These proteins and pathways played a critical role in the regulation of cell cycle, apoptosis, autophagy, EMT, and ROS generation. These findings suggest that vancomycin-induced proteomic responses in HK-2 cells involvefunctional proteins and pathways that regulate cell cycle, apoptosis, autophagy, and redox homeostasis. This is the first systemic study revealed the networks of signaling pathways and proteomic responses to vancomycin treatment in HK-2 cells, and the data may be used to discriminate the molecular and clinical subtypes and to identify new targets and biomarkers for vancomycin-induced nephrotoxic effect. Further studies are warranted to explore the potential of quantitative proteomic analysis in the identification of new targets and biomarkers for drug-induced renal toxicity.
authors: Department of Pharmacy, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai 200040, China. lizhiling22@163.com.
authors: Zhi-Ling
authors: ZL
authors: Li
authors: Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33612, USA. szhou@health.usf.edu.
authors: Shu-Feng
authors: SF
authors: Zhou
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D018929:Cell Culture Techniques; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D007687:Kidney Tubules, Proximal / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020543:Proteome / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014640:Vancomycin / Q000633:toxicity*
chemical_list: D000596:Amino Acids; D020543:Proteome; D014640:Vancomycin
keywords: SILAC; nephrotoxicity; proteomics; vancomycin