Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells.

Comparative proteomic analysis of SLC13A5 knockdown reveals elevated ketogenesis and enhanced cellular toxic response to chemotherapeutic agents in HepG2 cells. Toxicol Appl Pharmacol. 2020 Jul 04;:115117 Authors: Hu T, Huang W, Li Z, Kane MA, Zhang L, Huang SM, Wang H Abstract Solute carrier family 13 member 5 (SLC13A5) is an uptake transporter mainly expressed in the liver and transports citrate from blood circulation into hepatocytes. Accumulating evidence suggests that SLC13A5 is involved in hepatic lipogenesis, cell proliferation, epilepsy, and bone development in mammals. However, the molecular mechanisms behind SLC13A5-mediated physiological/pathophysiological changes are largely unknown. In this regard, we conducted a differential proteome analysis in HepG2 and SLC13A5-knockdown (KD) HepG2 cells. A total of 3826 proteins were quantified and 330 proteins showed significant alterations (fold change ≥1.5; p < .05) in the knockdown cells. Gene ontology enrichment analysis reveals that 38 biological processes were significantly changed, with ketone body biosynthetic process showing the most significant upregulation following SLC13A5-KD. Catalytic activity and binding activity were the top two molecular functions associated with differentially expressed proteins, while HMG-CoA lyase activity showed the highest fold enrichment. Further ingenuity pathway analysis predicted 40 canonical pathways and 28 upstream regulators (pâ...
Source: Toxicology and Applied Pharmacology - Category: Toxicology Authors: Tags: Toxicol Appl Pharmacol Source Type: research