PMID- 12110510
OWN - NLM
STAT- MEDLINE
DCOM- 20020808
LR  - 20161124
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 283
IP  - 2
DP  - 2002 Aug
TI  - LPA is a novel lipid regulator of mesangial cell hexokinase activity and HKII 
      isoform expression.
PG  - F271-9
AB  - The prototypical extracellular phospholipid mediator, lysophosphatidic acid 
      (LPA), exhibits growth factor-like properties and represents an important 
      survival factor in serum. This potent mesangial cell mitogen is increased in 
      conditions associated with glomerular injury. It is also a known activator of the 
      classic mitogen-activated protein kinase (MAPK) pathway, which plays an important 
      role in the regulation of mesangial cell hexokinase (HK) activity. To better 
      understand the mechanisms coupling metabolism to injury, we examined the ability 
      of LPA to regulate HK activity and expression in cultured murine mesangial cells. 
      LPA increased total HK activity in a concentration- and time-dependent manner, 
      with maximal increases of >50% observed within 12 h of exposure to LPA 
      concentrations > or =25 microM (apparent ED(50) 2 microM). These effects were 
      associated with increased extracellular signal-regulated kinase (ERK) activity 
      and were prevented by the pharmacological inhibition of either MAPK/ERK kinase or 
      protein kinase C (PKC). Increased HK activity was also associated with increased 
      glucose (Glc) utilization and lactate accumulation, as well as selectively 
      increased HKII isoform abundance. The ability of exogenous LPA to increase HK 
      activity was both Ca2+ independent and pertussis toxin insensitive and was 
      mimicked by LPA-generating phospholipase A2. We conclude that LPA constitutes a 
      novel lipid regulator of mesangial cell HK activity and Glc metabolism. This 
      regulation requires sequential activation of both Ca2+-independent PKC and the 
      classic MAPK pathway and culminates in increased HKII abundance. These previously 
      unrecognized metabolic consequences of LPA stimulation have both physiological 
      and pathophysiological implications. They also suggest a novel mechanism whereby 
      metabolism may be coupled to cellular injury via extracellular lipid mediators.
FAU - Coy, Platina E
AU  - Coy PE
AD  - Section of Nephrology, Department of Medicine, University of Illinois at Chicago 
      College of Medicine, Chicago, Illinois 60612-7315, USA.
FAU - Taneja, Navin
AU  - Taneja N
FAU - Lee, Iris
AU  - Lee I
FAU - Hecquet, Claudie
AU  - Hecquet C
FAU - Bryson, Jane M
AU  - Bryson JM
FAU - Robey, R Brooks
AU  - Robey RB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Carcinogens)
RN  - 0 (Isoenzymes)
RN  - 0 (Lysophospholipids)
RN  - 0 (Phorbol Esters)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 33X04XA5AT (Lactic Acid)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - IY9XDZ35W2 (Glucose)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Carcinogens/pharmacology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Glomerular Mesangium/*cytology/*enzymology
MH  - Glucose/metabolism
MH  - Hexokinase/*metabolism
MH  - Isoenzymes/*metabolism
MH  - Lactic Acid/biosynthesis
MH  - Lysophospholipids/*pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Pertussis Toxin
MH  - Phorbol Esters/pharmacology
MH  - Phospholipases A/pharmacology
MH  - Phospholipases A2
MH  - Protein Kinase C/antagonists & inhibitors/metabolism
MH  - Virulence Factors, Bordetella/pharmacology
EDAT- 2002/07/12 10:00
MHDA- 2002/08/09 10:01
CRDT- 2002/07/12 10:00
PHST- 2002/07/12 10:00 [pubmed]
PHST- 2002/08/09 10:01 [medline]
PHST- 2002/07/12 10:00 [entrez]
AID - 10.1152/ajprenal.00093.2001 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2002 Aug;283(2):F271-9. doi: 
      10.1152/ajprenal.00093.2001.