PMID- 18614816
OWN - NLM
STAT- MEDLINE
DCOM- 20090114
LR  - 20211020
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 49
IP  - 11
DP  - 2008 Nov
TI  - Cannabinoid (CB2) receptor deficiency reduces the susceptibility of macrophages 
      to oxidized LDL/oxysterol-induced apoptosis.
PG  - 2338-46
LID - 10.1194/jlr.M800105-JLR200 [doi]
AB  - Macrophage apoptosis is an important process in the pathophysiology of 
      atherosclerosis. Oxidized low-density lipoproteins (OxLDL) are a major component 
      of lesions and potently induce macrophage apoptosis. Cannabinoid receptor 2 
      (CB2), the predominant macrophage cannabinoid receptor, modulates several 
      macrophage processes associated with ongoing atherosclerosis; however, the role 
      of CB2 in macrophage apoptosis is unknown. To determine if CB2 influences a 
      macrophage apoptotic pathway relevant to atherosclerosis, we examined the effect 
      of CB2 deficiency on OxLDL-induced macrophage apoptosis. In situ terminal 
      transferase-mediated dUTP nick end labeling (TUNEL) analysis of resident 
      peritoneal macrophages detected significantly fewer apoptotic CB2(-/-) 
      macrophages than CB2(+/+) macrophages after incubation with OxLDL (27.9 +/- 4.7% 
      vs. 61.9 +/- 8.5%, P < 0.001) or 7-ketocholesterol (7KC) (18.9 +/- 10.5% vs. 54.1 
      +/- 6.9%, P < 0.001), an oxysterol component of OxLDL. Caspase-3 activity; 
      proteolytic conversion of procaspase-3; and cleavage of a caspase-3 substrate, 
      PARP, were also diminished in 7KC-treated CB2(-/-) macrophages. Furthermore, the 
      deactivation of the prosurvival kinase, Akt, in response to 7KC was impaired in 
      CB2(-/-) macrophages. These results suggest that CB2 expression increases the 
      susceptibility of macrophages to OxLDL-induced apoptosis, in part, by modulating 
      the effect of oxysterols on the Akt survival pathway and that CB2 may influence 
      atherosclerosis by modulating lesional macrophage apoptosis.
FAU - Freeman-Anderson, Natalie E
AU  - Freeman-Anderson NE
AD  - Department of Biochemistry and Molecular Biology, James H. Quillen College of 
      Medicine, East Tennessee State University, Johnson City, TN, USA.
FAU - Pickle, Theresa G
AU  - Pickle TG
FAU - Netherland, Courtney D
AU  - Netherland CD
FAU - Bales, Alicia
AU  - Bales A
FAU - Buckley, Nancy E
AU  - Buckley NE
FAU - Thewke, Douglas P
AU  - Thewke DP
LA  - eng
GR  - R15 HL085137/HL/NHLBI NIH HHS/United States
GR  - HL085137/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080709
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - 0 (oxidized low density lipoprotein)
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Atherosclerosis/genetics/metabolism
MH  - Cells, Cultured
MH  - DNA Fragmentation
MH  - Humans
MH  - In Situ Nick-End Labeling
MH  - Lipoproteins, LDL/*physiology
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oxidation-Reduction
MH  - Receptor, Cannabinoid, CB2/*deficiency/genetics
PMC - PMC2563213
EDAT- 2008/07/11 09:00
MHDA- 2009/01/15 09:00
PMCR- 2009/11/01
CRDT- 2008/07/11 09:00
PHST- 2008/07/11 09:00 [pubmed]
PHST- 2009/01/15 09:00 [medline]
PHST- 2008/07/11 09:00 [entrez]
PHST- 2009/11/01 00:00 [pmc-release]
AID - S0022-2275(20)34611-3 [pii]
AID - jlr49112338 [pii]
AID - 10.1194/jlr.M800105-JLR200 [doi]
PST - ppublish
SO  - J Lipid Res. 2008 Nov;49(11):2338-46. doi: 10.1194/jlr.M800105-JLR200. Epub 2008 
      Jul 9.