4.3 Article

Preconditioning With Tauroursodeoxycholic Acid Protects Against Contrast-Induced HK-2 Cell Apoptosis by Inhibiting Endoplasmic Reticulum Stress

Journal

ANGIOLOGY
Volume 66, Issue 10, Pages 941-949

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1177/0003319715575965

Keywords

contrast-induced acute kidney injury; tauroursodeoxycholic acid; contrast media; apoptosis; endoplasmic reticulum stress

Funding

  1. National Natural Science Foundation of China [81270285, 81100198]
  2. Training Program Foundation for the Talents by Beijing Municipal Organization Department [2012D003034000016]
  3. Beijing Municipal High-Level Talent Foundation of Health System [2011-1-5]
  4. Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZY201303]
  5. National Key Clinical Speciality Construction Project

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To investigate whether tauroursodeoxycholic acid (TUDCA) could attenuate contrast media (CM)-induced renal tubular cell apoptosis by inhibiting endoplasmic reticulum stress (ERS), we exposed HK-2 cells to increasing doses of meglumine diatrizoate (20, 40, and 80 mg I/mL) for 2 to 16 hours, with/without TUDCA preconditioning for 24 hours. Cell viability test, Hoechst 33258 staining, and flow cytometry were used to detect meglumine diatrizoate-induced cell apoptosis, while real-time polymerase chain reaction and Western blot analysis were used to measure the expressions of ERS markers of glucose-regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), and the apoptosis-related marker of caspase 12. Cell apoptosis and messenger RNA (mRNA) expression of GRP78 (P = .005), ATF4 (P = .01), and caspase 12 (P = .001) were significantly higher in the CM 4 hours group than the control as well as the protein expressions. The TUDCA preconditioning reduced the mRNA expression of GRP78, ATF4, and caspase 12 in the CM 4 hours groups (P = .009, .019, and .003, respectively) as well as the protein expression. In conclusion, TUDCA could protect renal tubular cells from meglumine diatrizoate-induced apoptosis by inhibiting ERS.

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