Pemphigus serum and captopril induce heat shock protein 70 and inducible nitric oxide synthase overexpression, triggering apoptosis in human keratinocytes

Summary Background  Captopril is an angiotensin‐converting enzyme inhibitor with sulphydryl groups in its chemical structure. It is commonly used as an antihypertensive drug. The occurrence of pemphigus vulgaris has repeatedly been reported in patients receiving captopril. The capacity of captopril...

Full description

Saved in:
Bibliographic Details
Published in:British journal of dermatology (1951) 2004-06, Vol.150 (6), p.1070-1080
Main Authors: Baroni, A., Buommino, E., Paoletti, I., Orlando, M., Ruocco, E., Ruocco, V.
Format: Article
Language:English
Subjects:
Angiotensin-Converting Enzyme Inhibitors - adverse effects
Angiotensin-Converting Enzyme Inhibitors - pharmacology
Apoptosis
Autoantibodies - pharmacology
Biological and medical sciences
Blotting, Western - methods
Bullous diseases of the skin
captopril
Captopril - adverse effects
Captopril - pharmacology
Cells, Cultured
Culture Media, Conditioned
Cytoskeleton - drug effects
Cytoskeleton - ultrastructure
Dermatology
DNA Fragmentation
Dose-Response Relationship, Drug
Enalapril - adverse effects
Enalapril - pharmacology
Enzyme Activation
heat shock protein 70
HSP70 Heat-Shock Proteins - analysis
Humans
inducible nitric oxide synthase
Keratinocytes - drug effects
Keratinocytes - metabolism
Keratinocytes - pathology
Medical sciences
Microscopy, Fluorescence
Nitric Oxide Synthase - analysis
Nitric Oxide Synthase Type II
Nitrites - analysis
pemphigus
Pemphigus - chemically induced
Pemphigus - immunology
Pemphigus - pathology
Proto-Oncogene Proteins c-myc - analysis
Reverse Transcriptase Polymerase Chain Reaction
Transglutaminases - analysis
Tumor Suppressor Protein p53 - analysis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Background  Captopril is an angiotensin‐converting enzyme inhibitor with sulphydryl groups in its chemical structure. It is commonly used as an antihypertensive drug. The occurrence of pemphigus vulgaris has repeatedly been reported in patients receiving captopril. The capacity of captopril and pemphigus serum to induce acantholysis, in vivo or in vitro, has been demonstrated experimentally. Objectives  To show that captopril and pemphigus serum, acting by a biochemical and immunological mechanism, respectively, trigger apoptosis. Methods  Human keratinocyte cells were treated with 15 mmol L−1 captopril or with pemphigus serum. DNA was extracted and the terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end labelling method was used to detect apoptosis. Results  DNA fragmentation occurred after 72 h of treatment. Increased expression of p53, c‐myc and inducible nitric oxide (NO) synthase (iNOS) mRNA were observed by polymerase chain reaction (PCR) in the treated cells compared with the untreated ones. The increase in iNOS gene expression was associated with overproduction of NO. Moreover, the addition of 1 mmol L−1N‐monomethyl‐L‐arginine, a structural analogue of arginine, reduced nitrite levels by about 70% in cells treated with captopril or pemphigus serum. Western blot analysis revealed an overexpression of heat shock protein 70 (hsp70) in cells treated with captopril or pemphigus serum. Finally, total inhibition of the keratinocyte transglutaminase gene was shown by PCR analysis in the same samples, compared with control cells. Conclusions  These data demonstrate the involvement of apoptosis in keratinocytes treated with captopril or pemphigus serum, with induction of the iNOS gene and hsp70 in the cascade of events leading to programmed cell death.
ISSN:0007-0963
1365-2133
DOI:10.1111/j.1365-2133.2004.05919.x