PSTK exerts protective role in cisplatin-tubular cell injury via BAX/BCL2/Caspase3 pathway

Physiol Rep. 2025 Jan;13(1):e70162. doi: 10.14814/phy2.70162.

Abstract

Cisplatin is a widely used anticancer drug, but its accumulation in renal tubular epithelial cells (TECs) can cause acute kidney injury. Phosphoseryl-tRNA kinase (PSTK) is an intermediate product produced under oxidative stress conditions. This study aimed to elucidate whether PSTK could protect TECs and its possible mechanisms. We found that PSTK levels decreased after cisplatin treatment, but PSTK overexpression using lentivirus vectors protected TEC viability. Overexpression of PSTK increased selenoprotein concentrations and reduced intracellular ROS levels. Additionally, PSTK overexpression inhibited the BAX/BCL2/Caspase 3 pathway after cisplatin stimulation, suggesting its potential role in preventing cell apoptosis. Taken together, this study suggests that PSTK could protect TEC viability from cisplatin-induced injury, possibly by inhibiting mitochondrial apoptosis. The study is significant for developing therapeutic strategies that could manipulate PSTK to delay AKI progression.

Keywords: AKI; PSTK; apoptosis; cisplatin; oxidative stress.

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / toxicity
  • Apoptosis* / drug effects
  • Caspase 3* / genetics
  • Caspase 3* / metabolism
  • Cell Line
  • Cisplatin* / pharmacology
  • Cisplatin* / toxicity
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Kidney Tubules / pathology
  • Proto-Oncogene Proteins c-bcl-2* / genetics
  • Proto-Oncogene Proteins c-bcl-2* / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • bcl-2-Associated X Protein* / genetics
  • bcl-2-Associated X Protein* / metabolism

Substances

  • Cisplatin
  • bcl-2-Associated X Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Caspase 3
  • Antineoplastic Agents
  • Reactive Oxygen Species