Increased oxidative stress in scavenger receptor BI knockout mice with dysfunctional HDL.
OBJECTIVE
In the current study the effect of disruption of SR-BI, a prominent regulator of HDL metabolism, on the activity of the HDL-associated antioxidant enzymes PON1 and PAF-AH as well as in vivo oxidative stress were investigated.


RESULTS
SR-BI deficiency resulted in 1.4-fold (P<0.001) and 1.6-fold (P<0.01) lower serum paraoxonase and arylesterase activity of PON1, respectively. Furthermore, a trend to slightly lower PAF-AH activity was observed. In vivo oxidative stress was evaluated by measuring isoprostane F2alpha-VI (iPF2alpha-VI) and protein carbonyls. Compared with wild-type animals, SR-BI knockouts had 1.4-fold (P<0.05) higher levels of plasma iPF2alpha-VI, whereas urinary excretion was increased 2-fold (P<0.0001). Plasma carbonyls were 1.5-fold (P<0.05) higher in SR-BI knockout animals. Furthermore, iPF2alpha-VI and carbonyl levels were 2.1-fold (P<0.01) and 1.4-fold (P<0.01), respectively, increased in livers of SR-BI knockout mice, and in reaction to the increased oxidative stress the expression of several endogenous antioxidant systems was upregulated. On challenging the SR-BI knockout mice with an atherogenic Western-type diet, a further increase in oxidative stress in these animals was observed.


CONCLUSIONS
SR-BI deficiency results in a reduced activity of the antioxidant enzyme PON1 and a significant increase in oxidative stress, potentially contributing to the proatherogenic effect of SR-BI deficiency.
Van Eck
Miranda
M
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands. m.eck@LACDR.LeidenUniv.nl
Hoekstra
Menno
M
Hildebrand
Reeni B
RB
Yaong
Yuemang
Y
Stengel
Dominique
D
Kruijt
J Kar
JK
Sattler
Wolfgang
W
Tietge
Uwe J F
UJ
Ninio
Ewa
E
Van Berkel
Theo J C
TJ
Praticò
Domenico
D
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood* / Q000378:metabolism; D000818:Animals; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000378:metabolism; D004036:Diet, Atherogenic; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D051122:Scavenger Receptors, Class B / Q000235:genetics*
C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D043303:Aryldialkylphosphatase