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I Toda, I Saito, K Yamada, Y Hayashi, K Tsubota; Alternative Cleavage of -fodrin, Organ-specific Autoantigen in Lacrimal Gland in Sjogren's Symdrome . Invest. Ophthalmol. Vis. Sci. 2002;43(13):73.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: An 120-kD a-fodrin has been identified as a candidate organ-specific autoantigen in salivary gland (SG) of SS. We have detected different size of a-fodrin fragments in lacrimal gland (LG) of mouse models of SS (1999, ARVO) The purpose of this study was to determine the mechanism of a-fodrin cleavage in LG. Methods: 1) LG and SG from NFS/sld 3Tx (SS) and NFS/sld non-Tx (non-SS) mice were homogenized in lysis buffer, separated on SDS-PAGE, and reacted with serum from NFS/sld 3Tx mouse. 2) LG and SG cell lines established from p53 knockout mice were induced apoptosis with anti-fas antibody, staurosporin or TGF-ß. These cells were processed for measurement of enzymatic activities of caspase -3, -6, and -9. and for immunoblotting with anti-a-fodrin antibody. Results: 1) A 64-kD a-fodrin fragment was detected in LG of NFS/sld 3Tx mouse, but not in SG of NFS/sld 3Tx, and LG and SG of NFS/sld non Tx mice. 2) A 64-kD a-fodrin was detected only in LG when apoptosis was induced by staurosporin. Time course and increased level of caspase-3 activity after induction of apoptosis was different between LG and SG. Conclusion: Distinguish enzymatic reactivity against different apoptotic stimuli in LG may cause alternative cleavage of a-fodrin. Inhibition of LG-specific apoptotic pathway may be a therapeutic strategy for autoimmune destruction of LG in SS.
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