PMID- 19497347
OWN - NLM
STAT- MEDLINE
DCOM- 20091013
LR  - 20131121
IS  - 1638-6183 (Electronic)
IS  - 0300-9084 (Linking)
VI  - 91
IP  - 8
DP  - 2009 Aug
TI  - Peroxisome proliferator-activated receptor alpha (PPARalpha) agonists 
      down-regulate alpha2-macroglobulin expression by a PPARalpha-dependent mechanism.
PG  - 1029-35
LID - 10.1016/j.biochi.2009.05.007 [doi]
AB  - Fibrates are peroxisome proliferator-activated receptor alpha (PPARalpha) ligands 
      used to normalize lipid and glucose parameters and exert anti-inflammatory 
      effects. The acute-phase response (APR) is an important inflammatory process. One 
      of the most important acute-phase proteins in rats is alpha2-macroglobulin 
      (A2Mg). Whereas normal adult rats present low serum levels, pregnant rats display 
      high amounts. Therefore, we used pregnant rats to detect the effect of 
      fenofibrate on hepatic A2Mg expression by RT-PCR and Northern blot. Virgin rats 
      were used as controls. The expression of other APR genes, a known 
      fibrate-responder gene, gamma-chain fibrinogen (gamma-Fib), and one gene from the 
      same family as A2Mg, complement component 3 (C3), were also measured in liver. In 
      order to determine whether the fibrate-effects were mediated by PPARalpha, 
      wild-type mice and PPARalpha-null mice were also used and treated with WY-14,643 
      (WY) or di-2-ethylhexyl phthalate (DEHP). Fenofibrate depressed A2Mg expression 
      in virgin rats, but expression was decreased more sharply in pregnant rats. 
      Expression of C3 and gamma-Fib was diminished after treatment only in pregnant 
      rats. On the other hand, WY, but not DEHP, reduced A2Mg and gamma-Fib expression 
      in the livers of wild-type mice, without any effect in PPARalpha-null mice. WY or 
      DEHP did not affect C3 expression. Therefore, A2Mg expression is modified by 
      PPARalpha agonists not only in pregnant rats under augmented APR protein 
      synthesis, but also in virgin rats and mice under basal conditions. 
      Interestingly, our results also identify A2Mg as a novel PPARalpha 
      agonist-regulated gene.
FAU - Gonzalez, Maria del Carmen
AU  - Gonzalez MC
AD  - Universidad San Pablo-CEU, Madrid, Spain.
FAU - Corton, J Christopher
AU  - Corton JC
FAU - Cattley, Russell C
AU  - Cattley RC
FAU - Herrera, Emilio
AU  - Herrera E
FAU - Bocos, Carlos
AU  - Bocos C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090602
PL  - France
TA  - Biochimie
JT  - Biochimie
JID - 1264604
RN  - 0 (PPAR alpha)
RN  - 0 (alpha-Macroglobulins)
RN  - U202363UOS (Fenofibrate)
SB  - IM
MH  - Animals
MH  - Down-Regulation/*drug effects
MH  - Female
MH  - Fenofibrate/*pharmacology
MH  - Male
MH  - Mice
MH  - PPAR alpha/*agonists/metabolism
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sexual Abstinence
MH  - alpha-Macroglobulins/*genetics
EDAT- 2009/06/06 09:00
MHDA- 2009/10/14 06:00
CRDT- 2009/06/06 09:00
PHST- 2009/02/25 00:00 [received]
PHST- 2009/05/20 00:00 [accepted]
PHST- 2009/06/06 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/10/14 06:00 [medline]
AID - S0300-9084(09)00148-5 [pii]
AID - 10.1016/j.biochi.2009.05.007 [doi]
PST - ppublish
SO  - Biochimie. 2009 Aug;91(8):1029-35. doi: 10.1016/j.biochi.2009.05.007. Epub 2009 
      Jun 2.