Activated caspase 3 and cleaved poly(ADP-ribose)polymerase in salivary epithelium suggest a pathogenetic mechanism for Sjögren's syndrome.
OBJECTIVE
Apoptosis is an organized energy-dependent process of cellular self-destruction carried out by proteolytic enzymes such as the caspases. These enzymes may play a role in epithelial cell apoptosis in Sjögren's syndrome (SS). A classical caspase substrate is poly(ADP-ribose)polymerase (PARP), a DNA repair enzyme. To elucidate the molecular mechanisms responsible for salivary gland dysfunction in SS, we studied the expression of caspase and PARP in SS salivary gland biopsies.


METHODS
The presence of activated caspases (caspases 3 and 9) and cleaved PARP (85 kDa) in SS biopsies was demonstrated by immunohistochemistry using specific polyclonal antibodies.


RESULTS
Initial studies performed with an antibody reagent that recognizes both active and inactive forms of caspase 3 identified this enzyme in SS salivary ductal and acinar cells. Activated caspase 3 and cleaved PARP were strongly expressed in ductal and acinar cells in SS salivary glands (13/15). Ductal and acinar cells from normal salivary glands (n=5) stained with less intensity compared with SS tissue. Staining for activated caspase 9 was negative in all samples. Likewise, infiltrating lymphocytes were negative for caspase 3, caspase 9 and cleaved PARP.


CONCLUSIONS
This study shows that caspase 3 is important in the salivary dysfunction of SS, while caspase 9 appears not to be involved.
Jimenez
F
F
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Aiba-Masago
S
S
Al Hashimi
I
I
Vela-Roch
N
N
Fernandes
G
G
Yeh
C-K
CK
Talal
N
N
Dang
H
H
D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D012469:Salivary Glands / Q000201:enzymology* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000201:enzymology* / Q000473:pathology
D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases