Pemphigus serum and captopril induce heat shock protein 70 and inducible nitric oxide synthase overexpression, triggering apoptosis in human keratinocytes.
Br J Dermatol
; 150(6): 1070-80, 2004 Jun.
Article
in En
| MEDLINE
| ID: mdl-15214891
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Angiotensin-Converting Enzyme Inhibitors
/
Captopril
/
Keratinocytes
/
Pemphigus
/
Apoptosis
/
HSP70 Heat-Shock Proteins
/
Nitric Oxide Synthase
Limits:
Humans
Language:
En
Journal:
Br J Dermatol
Year:
2004
Document type:
Article
Affiliation country:
Italia