PMID- 22687273
OWN - NLM
STAT- MEDLINE
DCOM- 20121204
LR  - 20191210
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 95
IP  - 3
DP  - 2012 Aug 1
TI  - PKCdelta signalling regulates SR-A and CD36 expression and foam cell formation.
PG  - 346-55
LID - 10.1093/cvr/cvs189 [doi]
AB  - AIMS: The formation of foam cells is crucial in the initiation and progression of 
      atherosclerosis. One of the critical steps in foam cell formation is the uptake 
      of low-density lipoprotein (LDL) by macrophages via scavenger receptors (SRs). 
      This study examined the role of protein kinase C (PKC) isoforms on foam cell 
      formation. METHODS AND RESULTS: The effects of short-hairpin RNA (shRNA) and 
      small interfering RNA (siRNA) against classical PKC and novel PKC isoforms were 
      investigated in THP-1-derived macrophages and primary macrophages. The knockdown 
      of PKCdelta inhibited oxidized LDL (OxLDL) uptake and intracellular cholesterol 
      accumulation in both cell models. The reduction of PKCdelta resulted in decreased 
      expression of SR-A and CD36. Similar conclusions were obtained in examining the 
      effects of a PKCdelta inhibitor, rottlerin. Molecular investigation revealed that a 
      decrease in PKCdelta inhibited protein kinase B (PKB/Akt) expression and 
      extracellular-signal-regulated kinase (ERK) phosphorylation. Surprisingly, 
      PKCdelta-knockdown selectively decreased protein but not the mRNA level of PKCbetaI and 
      PKCbetaII. We showed that the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt 
      upstream of ERK decreased SR-A and CD36 expression; however, the inhibition of 
      ERK or PKCbeta downstream of ERK attenuated SR-A but not CD36 expression. We further 
      demonstrated that PKCdelta could be induced by pro-atherogenic mediators, OxLDL and 
      interferon-gamma. Notably, PKCdelta, phosphorylated ERK, Akt, and SR-A were highly 
      expressed in human atherosclerotic arteries and CD68-positive macrophages as 
      visualized by immunohistochemical staining. CONCLUSION: Through regulating 
      PI3K/Akt and ERK activity, PKCdelta affects SR-A and CD36 expression and foam cell 
      formation. The results suggest PKCdelta as a potential target for atherosclerosis 
      therapeutics.
FAU - Lin, Chin-Sheng
AU  - Lin CS
AD  - Graduate Institute of Medical Science, National Defense Medical Center, No. 161 
      Sec. 6 Minquan E. Rd., Neihu, Taipei, Taiwan, ROC.
FAU - Lin, Feng-Yen
AU  - Lin FY
FAU - Ho, Ling-Jun
AU  - Ho LJ
FAU - Tsai, Chien-Sung
AU  - Tsai CS
FAU - Cheng, Shu-Mung
AU  - Cheng SM
FAU - Wu, Wan-Lin
AU  - Wu WL
FAU - Huang, Chuan-Yueh
AU  - Huang CY
FAU - Lian, Chen-Hao
AU  - Lian CH
FAU - Yang, Shih-Ping
AU  - Yang SP
FAU - Lai, Jenn-Haung
AU  - Lai JH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120611
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (CD36 Antigens)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (MSR1 protein, human)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Scavenger Receptors, Class A)
RN  - 0 (oxidized low density lipoprotein)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.13 (PRKCD protein, human)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.13 (Protein Kinase C beta)
RN  - EC 2.7.11.13 (Protein Kinase C-delta)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
CIN - Cardiovasc Res. 2013 Feb 1;97(2):389. PMID: 23172708
CIN - Cardiovasc Res. 2013 Feb 1;97(2):389-90. PMID: 23172709
MH  - Atherosclerosis/*enzymology/genetics/immunology
MH  - CD36 Antigens/genetics/*metabolism
MH  - Cell Line
MH  - Cholesterol/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Foam Cells/drug effects/*enzymology/immunology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Lipoproteins, LDL/metabolism
MH  - Macrophages/drug effects/*enzymology/immunology
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Protein Kinase C/metabolism
MH  - Protein Kinase C beta
MH  - Protein Kinase C-delta/antagonists & inhibitors/genetics/*metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA Interference
MH  - Scavenger Receptors, Class A/genetics/*metabolism
MH  - *Signal Transduction/drug effects
MH  - Transfection
EDAT- 2012/06/13 06:00
MHDA- 2012/12/10 06:00
CRDT- 2012/06/13 06:00
PHST- 2012/06/13 06:00 [entrez]
PHST- 2012/06/13 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
AID - cvs189 [pii]
AID - 10.1093/cvr/cvs189 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2012 Aug 1;95(3):346-55. doi: 10.1093/cvr/cvs189. Epub 2012 Jun 
      11.