Vitamin D inhibits captopril-induced cell detachment and apoptosis in keratinocytes.
BACKGROUND
Captopril, an angiotensin I-converting enzyme inhibitor, is a commonly prescribed antihypertensive drug. Its cutaneous side-effects include pemphigus vulgaris acantholysis and bullous pemphigoid-like cell-matrix detachment. This medication also triggers apoptosis in human keratinocytes. Calcitriol, the hormonally active vitamin D metabolite, protects keratinocytes from programmed cell death induced by various noxious stimuli.


OBJECTIVE
To examine if calcitriol protects proliferating keratinocytes from the damage inflicted by captopril.


METHODS
Autonomously proliferating HaCaT keratinocytes, used as a model for basal layer keratinocytes, were exposed to captopril. Cell detachment was examined visually by light microscopy. Cytotoxicity was assessed by Hoechst 33342 staining and lactate dehydrogenase release. Apoptotic death was assessed by monitoring caspase 3-like activity.


RESULTS
Cells exposed to captopril detached and became round. This process was accompanied by programmed cell death. From time-dependent monitoring of cell detachment and apoptosis, and examination of pan-caspase inhibitor effects on cell detachment we concluded that cell death is the consequence of cell detachment from the culture plate and not vice versa. Pretreatment with calcitriol significantly attenuated these events. The effects of calcitriol were already evident at 1 nmol L(-1) concentration of the hormone.


CONCLUSIONS
The results of this study show that calcitriol protects keratinocytes from captopril-induced cell detachment and apoptosis.
Zeeli
T
T
Department of Dermatology, Rabin Medical Center, Petah Tikva, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Langberg
M
M
Rotem
C
C
David
M
M
Koren
R
R
Ravid
A
A
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002216:Captopril / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D053148:Caspase 3 / Q000032:analysis; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D014807:Vitamin D / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D014807:Vitamin D; D002216:Captopril; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3