PMID- 23085347
OWN - NLM
STAT- MEDLINE
DCOM- 20130409
LR  - 20211203
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 215
IP  - 2
DP  - 2012 Nov 30
TI  - Amelioration of uremic toxin indoxyl sulfate-induced endothelial cell dysfunction 
      by Klotho protein.
PG  - 77-83
LID - S0378-4274(12)01335-5 [pii]
LID - 10.1016/j.toxlet.2012.10.004 [doi]
AB  - Indoxyl sulfate (IS), a common kind of uremic toxin, is considered as a risk 
      factor for aggravating endothelial function in CKD patients due to its oxidative 
      activity. The anti-aging protein Klotho, which is produced by the kidneys and 
      down-regulated in uremic conditions, has the ability to resist oxidative stress. 
      Here, we carried out an in vitro study to investigate the deleterious effects of 
      IS on endothelial cells and the protective role of Klotho protein. The cultured 
      human umbilical vein endothelial cells (HUVECs) were incubated with IS in the 
      presence or absence of Klotho protein. The release of reactive oxygen species 
      (ROS) and the expression of monocyte chemoattractant protein-1 (MCP-1) were 
      enhanced while the cell viability and production of nitric oxide (NO) were 
      inhibited by IS in a concentration-dependent manner. Meanwhile, the 
      phosphorylation of p38MAPK and the nuclear translocation of NF-kappaB were increased 
      in HUVECs treated with IS. Pretreatment with Klotho protein resulted in 
      remarkable increase of cell viability and decrease of ROS production in 
      IS-treated HUVECs. Like ROS scavenger, N-acetyl-l-cysteine (NAC), Klotho protein 
      could inhibit the IS-induced activations of p38MAPK and NF-kappaB. Moreover, Klotho 
      protein could also attenuate IS-induced reduction of NO production and 
      up-regulation of MCP-1 expression. These results suggest that IS can damage the 
      functions of endothelial cells. Klotho protein has the ability to ameliorate the 
      IS-induced endothelial dysfunction, which may be partly through inhibiting the 
      ROS/p38MAPK and downstream NF-kappaB signaling pathways.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Yang, Ke
AU  - Yang K
AD  - Institute of Nephrology of Chongqing and Department of Nephrology, Xinqiao 
      Hospital, Third Military Medical University, Chongqing 400037, China.
FAU - Nie, Ling
AU  - Nie L
FAU - Huang, Yunjian
AU  - Huang Y
FAU - Zhang, Jingbo
AU  - Zhang J
FAU - Xiao, Tangli
AU  - Xiao T
FAU - Guan, Xu
AU  - Guan X
FAU - Zhao, Jinghong
AU  - Zhao J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121017
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - EC 3.2.1.31 (Klotho Proteins)
RN  - N187WK1Y1J (Indican)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Flow Cytometry
MH  - Glucuronidase/*pharmacology
MH  - Human Umbilical Vein Endothelial Cells/*drug effects/metabolism/pathology
MH  - Humans
MH  - Immunoblotting
MH  - Indican/antagonists & inhibitors/*toxicity
MH  - Klotho Proteins
MH  - NF-kappa B/metabolism
MH  - Oxidative Stress/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Renal Insufficiency, Chronic/*metabolism/*pathology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2012/10/23 06:00
MHDA- 2013/04/10 06:00
CRDT- 2012/10/23 06:00
PHST- 2012/06/18 00:00 [received]
PHST- 2012/10/04 00:00 [revised]
PHST- 2012/10/08 00:00 [accepted]
PHST- 2012/10/23 06:00 [entrez]
PHST- 2012/10/23 06:00 [pubmed]
PHST- 2013/04/10 06:00 [medline]
AID - S0378-4274(12)01335-5 [pii]
AID - 10.1016/j.toxlet.2012.10.004 [doi]
PST - ppublish
SO  - Toxicol Lett. 2012 Nov 30;215(2):77-83. doi: 10.1016/j.toxlet.2012.10.004. Epub 
      2012 Oct 17.