Kidney Week

Abstract: TH-PO627

The Histone Deacetylase (HDAC) Inhibitor Belinostat Attenuates H₂O₂-Induced Senescence-Like State by Regulation of HDAC7 in the Human Renal Proximal Tubular Epithelial Cells

Session Information

• Health Maintenance, Nutrition, Metabolism - I
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Health Maintenance, Nutrition, and Metabolism

• 1300 Health Maintenance, Nutrition, and Metabolism

Authors

• Park, Jung Sun, Chonnam National University Medical School , Gwangju, Korea (the Republic of)

Jung Sun Park,

• Choi, Hoon In, Chonnam National University Hospital, Gwangju, Korea (the Republic of)

Hoon In Choi,

• Kim, Donghyun, Chonnam National University Hospital, Gwangju, Korea (the Republic of)

Donghyun Kim,

• Kim, Chang Seong, Chonnam National University Hospital, Gwangju, Korea (the Republic of)

Chang Seong Kim,

• Bae, Eun Hui, Chonnam National University Hospital, Gwangju, Korea (the Republic of)

Eun Hui Bae,

• Ma, Seong Kwon, Chonnam National University Medical School , Gwangju, Korea (the Republic of)

Seong Kwon Ma,

• Kim, Soo Wan, Chonnam National University Medical School , Gwangju, Korea (the Republic of)

Soo Wan Kim,

Background

Oxidative stress causes cell injury, disease, and aging. Renal aging is associated with decreased glomerular filtration rate, glomerulosclerosis, tubular atrophy, and fibrosis. HDAC7 modulates the cell cycle and induces cell senescence. We investigated the effect of HDAC inhibitor, belinostat on the H₂O₂-induced renal tubular senescence, and its underlying molecular mechanisms.

Methods

The effects of belinostat in H₂O₂-induced cell senescence was determined using human renal proximal tubular epithelial (HK-2) cells. H₂O₂-induced premature cellular senescence was detected by senescence-associated (SA)-β-gal staining and galactosidase activity, and the fluorescent dye 2’,7’-dichlorofluorescein diacetate was used to measure intracellular reactive oxygen species (ROS). Cell cycle progression was measured by flow cytometry and immunoblotting, and the knock down of histone deacetylases 7 was induced by HDAC7 siRNA.

Results

We observed the effect of belinostat on cell cycle regulation of HDAC7 in H₂O₂-induced senescence-like cells. H₂O₂ increased SA-b-gal staining and increased protein expression of HDAC7, p-caveolin-1, p-Rb, p-P53, p-P21 and P27. It also increased phosphorylation of p-AKT, p-ERK1 / 2, p-JNK, and induced ER stress. In contrast, pretreatment of belinostat reduced protein expression of HDAC7 and p-caveolin-1 and cell cycle-related protein expression and the phosphorylation of p-AKT, p-ERK1 / 2, and p-JNK and reduced ER stress expression. SiRNA treatment of HDAC7 inhibited the expression of p-caveolin-1 and decreased SA-b-gal staining.

Conclusion

Treatment of belinostat may exert anti-senescence effect by controlling p-AKT, p-ERK1/2, p-JNK, and ER stress signal pathways via inhibition of HDAC7 in H₂O₂-treated HK-2 cells.

Funding

• Government Support - Non-U.S.