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Involvement of ubiquitin-coding genes in cadmium-induced protein ubiquitination in human proximal tubular cells

Jin-Yong Lee1, Maki Tokumoto, Yasuyuki Fujiwara

  • 1Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University.

The Journal of Toxicological Sciences
|November 13, 2015
PubMed

Insights

Cadmium exposure increases ubiquitin-coding gene UBB expression, leading to more ubiquitinated proteins and cell toxicity. Reducing UBB lessens cadmium

Area of Science:

  • Toxicology
  • Molecular Biology
  • Cell Biology

Background:

  • Cadmium (Cd) is a toxic heavy metal causing kidney damage and protein aggregation.
  • Ubiquitin-conjugating enzyme genes are implicated in Cd toxicity.
  • The role of specific ubiquitin-coding genes in Cd toxicity is unclear.

Purpose of the Study:

  • Investigate the effect of Cd on ubiquitin-coding genes (UBB, UBC, UBA80, U52) in human kidney cells (HK-2).
  • Determine the role of UBB in Cd-induced cytotoxicity and protein ubiquitination.

Main Methods:

  • Treatment of HK-2 cells with Cadmium.
  • Quantitative analysis of UBB, UBC, UBA80, and U52 gene expression.
  • siRNA-mediated knockdown of UBB.
  • Assessment of cell viability and ubiquitinated protein levels.

Main Results:

  • Cd treatment increased UBB, UBC, and UBA80 expression before overt toxicity.
  • siRNA knockdown of UBB significantly reduced Cd-induced cell death.
  • Cd exposure elevated ubiquitinated protein levels, a process inhibited by UBB knockdown.

Conclusions:

  • UBB expression is upregulated by Cadmium in HK-2 cells.
  • Increased UBB contributes to Cadmium toxicity by promoting protein ubiquitination and accumulation.

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