2. Academic Validation
  3. Synaptotagmin-1 antagonizes paraquat intracellular accumulation and nephrocyte toxicity by up-regulating SERBP1/GLUT2 expression

Synaptotagmin-1 antagonizes paraquat intracellular accumulation and nephrocyte toxicity by up-regulating SERBP1/GLUT2 expression

  • Chem Biol Interact. 2024 Sep 1:400:111165. doi: 10.1016/j.cbi.2024.111165.
Ran Yin 1,  Jingjing Ke 2,  Mingming Zhao 1,  Yitian Ding 1,  Wenwen Li 3,  Mengxuan Li 1,  Lufeng Hu 4,  Xiaoqin Dai 5,  Guangliang Hong 6
Affiliations

Affiliations

  • 1 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Wenzhou Medical University, Wenzhou, 325000, China.
  • 2 Wenzhou Medical University, Wenzhou, 325000, China; Emergency Department, Taizhou First People's Hospital, Taizhou, 318020, China.
  • 3 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 4 Pharmacy Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 5 Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: dxq315@163.com.
  • 6 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Wenzhou Medical University, Wenzhou, 325000, China. Electronic address: honggl98@126.com.
PMID: 39059605 DOI: 10.1016/j.cbi.2024.111165
Abstract

Acute kidney injury (AKI) is common and an independent risk factor for mortality in patients with paraquat (PQ) poisoning. Currently, no specific antidote is available. Synaptotagmin-1 (SYT1) has been identified as a key protein that facilitates PQ efflux in PQ-resistant A549 cells, thereby preventing PQ-induced lung injury. However, the protective effect of STY1 on PQ-induced AKI remains to be elucidated. This study exposed human kidney 2 (HK-2) cells overexpressing SYT1 to PQ. These cells exhibited significantly lower levels of growth inhibition, Reactive Oxygen Species production, early Apoptosis, and PQ accumulation compared to the parent HK-2 cells. Transcriptomic screening and Western blot analysis revealed that SYT1 overexpression significantly promoted the expression of glucose transporter 2 (GLUT2). Inhibition of GLUT2 completely abolished the protective effects of SYT1 overexpression in HK-2 cells and restored intracellular PQ concentrations. Further immunoprecipitation-shotgun and RNA interference experiments revealed that SYT1 binds to and stabilizes the protein SERPINE1 mRNA-binding protein 1 (SERBP1), enhancing the stability of GLUT2 mRNA and its protein levels. In summary, SYT1 antagonizes PQ intracellular accumulation and prevents nephrocyte toxicity by up-regulating SERBP1/GLUT2 expression. This study identifies a potential target for the treatment of PQ-induced AKI.

Keywords

Acute kidney injury; Glucose transporter 2; Paraquat; SERPINE1 mRNA binding protein 1; Synaptotagmin-1.

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