PMID- 19158351
OWN - NLM
STAT- MEDLINE
DCOM- 20090326
LR  - 20240109
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 20
IP  - 3
DP  - 2009 Mar
TI  - Ketohexokinase-dependent metabolism of fructose induces proinflammatory mediators 
      in proximal tubular cells.
PG  - 545-53
LID - 10.1681/ASN.2008060576 [doi]
AB  - Increased consumption of fructose may play an important role in the epidemic of 
      metabolic syndrome and may presage the development of diabetes, cardiovascular 
      disease, and chronic kidney disease. Once in the cell, fructose is phosphorylated 
      by ketohexokinase (KHK), leading to consumption of ATP, formation of AMP, and 
      generation of uric acid through xanthine oxidoreductase (XOR). This study aimed 
      to examine the direct effects of fructose in human kidney proximal tubular cells 
      (HK-2) and whether they are mediated by the fructose metabolism via KHK. At a 
      similar concentration to that observed in peripheral blood after a meal, fructose 
      induced production of monocyte chemotactic protein 1 (MCP-1) and reactive oxygen 
      species in HK-2 cells. Knockdown of KHK by stable transfection with small hairpin 
      RNA demonstrated that these processes were KHK dependent. Several antioxidants, 
      including specific inhibitors of NADPH oxidase and XOR, prevented MCP-1 
      secretion. We detected XOR mRNA in HK-2 cells and confirmed its activity by 
      identifying uric acid by mass spectrometry. Fructose increased intracellular uric 
      acid, and uric acid induced production of MCP-1 as well. In summary, postprandial 
      concentrations of fructose stimulate redox- and urate-dependent inflammatory 
      mediators in proximal tubular cells.
FAU - Cirillo, Pietro
AU  - Cirillo P
AD  - Division of Nephrology, Hypertension and Transplantation, Department of Medicine, 
      University of Florida, Gainesville, FL 32610-0224, USA.
FAU - Gersch, Michael S
AU  - Gersch MS
FAU - Mu, Wei
AU  - Mu W
FAU - Scherer, Philip M
AU  - Scherer PM
FAU - Kim, Kyung Mee
AU  - Kim KM
FAU - Gesualdo, Loreto
AU  - Gesualdo L
FAU - Henderson, George N
AU  - Henderson GN
FAU - Johnson, Richard J
AU  - Johnson RJ
FAU - Sautin, Yuri Y
AU  - Sautin YY
LA  - eng
GR  - R01 HL068607/HL/NHLBI NIH HHS/United States
GR  - HL-68607/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090121
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA Primers)
RN  - 0 (Inflammation Mediators)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Reactive Oxygen Species)
RN  - 268B43MJ25 (Uric Acid)
RN  - 30237-26-4 (Fructose)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.17.1.4 (Xanthine Dehydrogenase)
RN  - EC 2.7.1.- (Fructokinases)
RN  - EC 2.7.1.3 (ketohexokinase)
SB  - IM
CIN - J Am Soc Nephrol. 2009 Mar;20(3):457-9. PMID: 19244571
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Chemokine CCL2/biosynthesis
MH  - DNA Primers/genetics
MH  - Fructokinases/antagonists & inhibitors/genetics/*metabolism
MH  - Fructose/*metabolism/pharmacology
MH  - Humans
MH  - Inflammation Mediators/*metabolism
MH  - Kidney Tubules, Proximal/drug effects/*metabolism
MH  - Male
MH  - Metabolic Syndrome/etiology/metabolism
MH  - Oxidation-Reduction
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Renal Insufficiency, Chronic/etiology/metabolism
MH  - Transfection
MH  - Uric Acid/pharmacology
MH  - Xanthine Dehydrogenase/genetics/metabolism
PMC - PMC2653686
EDAT- 2009/01/23 09:00
MHDA- 2009/03/27 09:00
PMCR- 2010/03/01
CRDT- 2009/01/23 09:00
PHST- 2009/01/23 09:00 [entrez]
PHST- 2009/01/23 09:00 [pubmed]
PHST- 2009/03/27 09:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - ASN.2008060576 [pii]
AID - 0576 [pii]
AID - 10.1681/ASN.2008060576 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2009 Mar;20(3):545-53. doi: 10.1681/ASN.2008060576. Epub 2009 
      Jan 21.