Kidney Week

Abstract: TH-PO758

Unveiling Protein-Protein Interaction of Maleic Acid-Induced AKI Using a Newly Developed Probe

Session Information

• Bioengineering
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

• 300 Bioengineering

Authors

• Lin, Hugo You-Hsien, University of California, Irvine, Irvine, United States

Hugo You-Hsien Lin,

• Liang, Shih-Shin, Kaohsiung Medical University, Kaohsiung, Taiwan

Shih-Shin Liang,

Background

Protein-Protein Interactions (PPIs) are important regulators of cellular metabolism and functions in physiology and pathology. However, it is challenging to decipher this complex interaction network of proteins in cells. Maleic acid (MA), an industrial raw material, was found to be illegally added as an emulsifier to starch-based food products by manufacturers in Taiwan in 2013. MA has been associated with renal dysfunction in many animal experiments. The goal of this study was to create a chemical probe that could detect MA-associated proteins in human renal proximal tubular cells that might be used for future detection and therapeutic targeting purposes.

Methods

Chemical probes were developed to investigate protein–protein interactions between MA and renal proteins. In the fabrication of these MA probes, we used silicon dioxide (SiO₂) modified with a silanized linker (3-aminopropyl triethoxyslane, APTES) to generate MA with APTES–SiO₂ particles. The probes were then incubated with the cell lysates of normal human kidney cell lines (HK-2) and subjected to MS/MS to identify several MA-related proteins. STITCH database was utilized to create a schematic illustration of the relationship among proteins associated with MA.

Results

We found nucleophosmin, neutral alpha-glucosidase AB, translocon-associated protein subunit alpha, elongation factor 1-gamma, 60S acidic ribosomal protein P0-like, and heat shock protein (HSP 90-alpha and beta) to be MA-associated proteins. These findings suggest that MA-induced acute kidney injury may come about as a result of regulation of protein transportation, cell processing, endoplasmic reticulum stress, ribosomal modulation and protein folding and unfolding.

Conclusion

The probes developed for this study can potentially be used to identify and detect the target proteins and help characterize a network of MA PPIs.