PMID- 32329444
OWN - NLM
STAT- MEDLINE
DCOM- 20200903
LR  - 20200903
IS  - 0231-5882 (Print)
IS  - 0231-5882 (Linking)
VI  - 39
IP  - 2
DP  - 2020 Mar
TI  - HDAC6 inhibitor Cay10603 inhibits high glucose-induced oxidative stress, 
      inflammation and apoptosis in retinal pigment epithelial cells via regulating 
      NF-kappaB and NLRP3 inflammasome pathway.
PG  - 169-177
LID - 10.4149/gpb_2019058 [doi]
AB  - The present study aimed to investigate the effects of histone deacetylase 6 
      (HDAC6) inhibitor Cay10603 (Cay) on high glucose (HG)-stimulated human retinal 
      pigment epithelium (RPE) cells and its underlying mechanisms. ARPE-19 cells were 
      cultured under normal glucose (NG) or high glucose (HG) conditions. The results 
      revealed that HDAC6 was upregulated in HG-stimulated ARPE-19 cells. Cay treatment 
      caused a decrease in intracellular reactive oxygen species (ROS). The levels of 
      malondialdehyde (MDA) and myeloperoxidase (MPO) were reduced accompanied by 
      increase in the activities of superoxide dismutase (SOD) and catalase (CAT) after 
      treatment with Cay. Besides, Cay decreased the levels of tumor necrosis factor-alpha 
      (TNF-alpha), interleukin-1beta (IL-1beta), IL-6 and monocyte chemoattractant protein-1 
      (MCP-1) in supernatant. Meanwhile, the apoptotic rate in Cay-treated ARPE-19 
      cells notably reduced, coupled with an upregulation in Bcl-2 expression and a 
      downregulation in cleaved caspase-3 and cleaved caspase-9 expression. Cay 
      decreased the expression of phospho (p)-NF-kappaB p65, p-IkappaB-alpha, NLRP3, cleaved 
      caspase-1 and ASC while increased the expression of NF-kappaB p65 (cytoplasm). Taken 
      together, these findings demonstrated that Cay suppressed HG-induced oxidative 
      stress, inflammation and apoptosis via regulating NF-kappaB and NLRP3 inflammasome 
      pathway in HG-induced ARPE-19 cells, suggesting that Cay might be a therapeutic 
      agent for the treatment of diabetic retinopathy.
FAU - Yang, Qingsong
AU  - Yang Q
AD  - Nanjing Tongren Eye Center, Nanjing Tongren Hosipital, Nanjing, Jiangsu, China.
FAU - Li, Sizhen
AU  - Li S
FAU - Zhou, Zixiu
AU  - Zhou Z
FAU - Fu, Min
AU  - Fu M
FAU - Yang, Xiaodong
AU  - Yang X
FAU - Hao, Kuanxiao
AU  - Hao K
FAU - Liu, Yating
AU  - Liu Y
LA  - eng
PT  - Journal Article
PL  - Slovakia
TA  - Gen Physiol Biophys
JT  - General physiology and biophysics
JID - 8400604
RN  - 0 (CAY10603)
RN  - 0 (Carbamates)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Inflammasomes)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Oxazoles)
RN  - 0 (Reactive Oxygen Species)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - *Apoptosis
MH  - Carbamates/*pharmacology
MH  - Epithelial Cells/cytology/*drug effects
MH  - Glucose
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Humans
MH  - Inflammasomes/*metabolism
MH  - Inflammation
MH  - NF-kappa B/*metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Oxazoles/*pharmacology
MH  - *Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
MH  - Retina/cytology
EDAT- 2020/04/25 06:00
MHDA- 2020/09/04 06:00
CRDT- 2020/04/25 06:00
PHST- 2019/11/11 00:00 [received]
PHST- 2019/12/03 00:00 [accepted]
PHST- 2020/04/25 06:00 [entrez]
PHST- 2020/04/25 06:00 [pubmed]
PHST- 2020/09/04 06:00 [medline]
AID - 10.4149/gpb_2019058 [doi]
PST - ppublish
SO  - Gen Physiol Biophys. 2020 Mar;39(2):169-177. doi: 10.4149/gpb_2019058.