ß-Hydroxybutyrate, a ketone body, reduces the cytotoxic effect of cisplatin via activation of HDAC5 in human renal cortical epithelial cells.
Life Sci
; 222: 125-132, 2019 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-30851335
ABSTRACT
AIMS:
ß-Hydroxybutyrate (ßOHB) is a metabolic intermediate that constitutes about 70% of ketone bodies produced in liver from oxidation of fatty acids released from adipose tissue. A recent study showed that ßOHB inhibits HDAC1, 3 and 4 (classes I and IIa) in human embryonic kidney 293 (HEK293) cells. Therefore, ßOHB could regulate epigenetics via modulating HDACs. However, little is known about the protective effect of ßOHB on renal cells through epigenetics. The aim of this study is to investigate whether ßOHB reduces cisplatin-induced nephrotoxicity in human renal cortical epithelial (HRCE) cells by modulating HDACs. MAINMETHODS:
In this study, we used human renal cortical epithelial (HRCE) cells. The anti-apoptotic effect of ßOHB was evaluated using flow cytometry analysis. The expression of apoptosis-related proteins and HDACs was evaluated by western immunoblot. KEYFINDINGS:
The results showed that ßOHB significantly reduced cisplatin-induced apoptosis in HRCE cells. Furthermore, ßOHB significantly reduced cisplatin-induced cleavage of caspase-3, acetylation of histone H3, and phosphorylation of AMP-activated kinase. This anti-apoptotic effect of ßOHB was markedly attenuated by an inhibitor of HDAC4/5, and ßOHB-mediated suppression of cleavage of caspase3 was significantly blocked by siRNA-induced gene silencing of HDAC5.SIGNIFICANCE:
ßOHB attenuates cisplatin-induced apoptosis by activation of HDAC5 in HRCE cells, suggesting that ßOHB may be a new therapeutic agent for cisplatin nephropathy.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cisplatin
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3-Hydroxybutyric Acid
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Epithelial Cells
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Histone Deacetylases
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Ketone Bodies
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Kidney Cortex
Limits:
Animals
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Humans
/
Male
Language:
En
Journal:
Life Sci
Year:
2019
Type:
Article