PMID- 15944340
OWN - NLM
STAT- MEDLINE
DCOM- 20060203
LR  - 20131121
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 16
IP  - 8
DP  - 2005 Aug
TI  - N-acetylcysteine decreases angiotensin II receptor binding in vascular smooth 
      muscle cells.
PG  - 2346-53
AB  - Antioxidants seem to inhibit angiotensin II (Ang II) actions by consuming 
      stimulated reactive oxygen species. An alternative hypothesis was investigated: 
      Antioxidants that are also strong reducers of disulfide bonds inhibit the binding 
      of Ang II to its surface receptors with consequent attenuation of signal 
      transduction and cell action. Incubation of cultured vascular smooth muscle 
      cells, which possess Ang II type 1a receptors, with the reducing agent 
      n-acetylcysteine (NAC) for 1 h at 37 degrees C resulted in decreased Ang II 
      radioligand binding in a concentration-dependent pattern. NAC removal restored 
      Ang II binding within 30 min. Incubation with n-acetylserine, a nonreducing 
      analogue of NAC, did not lower Ang II binding, and oxidized NAC was less 
      effective than reduced NAC in lowering Ang II binding. NAC did not decrease Ang 
      II type 1a receptor protein content. Other antioxidants regulated Ang II 
      receptors differently: alpha-Lipoic acid lowered Ang II binding after 24 h, and 
      vitamin E did not lower Ang II binding at all. NAC inhibited Ang II binding in 
      cell membranes at 21 or 37 but not 4 degrees C. Dihydrolipoic acid (the reduced 
      form of alpha-lipoic acid), which contains free sulfhydryl groups as NAC does, 
      decreased Ang II receptor binding in cell membranes, whereas alpha-lipoic acid, 
      which does not contain free sulfhydryl groups, did not. Ang II-stimulated 
      inositol phosphate formation was decreased by preincubation with NAC (1 h) or 
      alpha-lipoic acid (24 h) but not vitamin E. In conclusion, certain antioxidants 
      that are reducing agents lower Ang II receptor binding, and Ang II-stimulated 
      signal transduction is decreased in proportion to decreased receptor binding.
FAU - Ullian, Michael E
AU  - Ullian ME
AD  - Medical University of South Carolina, Division of Nephrology, CSB 829, 96 
      Jonathan Lucas Street, P.O. Box 250623, Charleston, SC 29425, USA. 
      ullianme@musc.edu
FAU - Gelasco, Andrew K
AU  - Gelasco AK
FAU - Fitzgibbon, Wayne R
AU  - Fitzgibbon WR
FAU - Beck, C Nicole
AU  - Beck CN
FAU - Morinelli, Thomas A
AU  - Morinelli TA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050608
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Antioxidants)
RN  - 0 (Disulfides)
RN  - 0 (Inositol Phosphates)
RN  - 0 (Phosphates)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 0 (Receptors, Angiotensin)
RN  - 1406-18-4 (Vitamin E)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 73Y7P0K73Y (Thioctic Acid)
RN  - 7NV2KHU5JA (dihydrolipoic acid)
RN  - S88TT14065 (Oxygen)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*pharmacology
MH  - Animals
MH  - Antioxidants/chemistry/pharmacology
MH  - Cell Membrane/metabolism
MH  - Disulfides
MH  - Dose-Response Relationship, Drug
MH  - Green Fluorescent Proteins/metabolism
MH  - Immunoblotting
MH  - Inositol Phosphates/chemistry
MH  - Kinetics
MH  - Male
MH  - Muscle, Smooth, Vascular/*cytology
MH  - Myocytes, Smooth Muscle/*metabolism
MH  - Oxygen/chemistry
MH  - Phosphates/chemistry
MH  - Protein Binding
MH  - Radioligand Assay
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species
MH  - Receptor, Angiotensin, Type 1/metabolism
MH  - Receptors, Angiotensin/*metabolism
MH  - Signal Transduction
MH  - Temperature
MH  - Thioctic Acid/analogs & derivatives/chemistry
MH  - Time Factors
MH  - Vitamin E/chemistry
EDAT- 2005/06/10 09:00
MHDA- 2006/02/04 09:00
CRDT- 2005/06/10 09:00
PHST- 2005/06/10 09:00 [pubmed]
PHST- 2006/02/04 09:00 [medline]
PHST- 2005/06/10 09:00 [entrez]
AID - ASN.2004060458 [pii]
AID - 10.1681/ASN.2004060458 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2005 Aug;16(8):2346-53. doi: 10.1681/ASN.2004060458. Epub 2005 
      Jun 8.