Elevated proapoptotic bax and caspase 3 activation in the NOD.scid model of Sjögren's syndrome

Reiji Masago, Sonomi Aiba-Masago, Norman Talal, Fabio Jimenez Zuluaga, Ibtisam Al-Hashimi, Michael Moody, C. Allen Lau, Ammon B. Peck, Jason Brayer, Michael G. Humphreys-Beher, Howard Dang

Research output: Contribution to journalArticle

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Abstract

Objective. Salivary gland epithelial cells in patients with Sjögren's syndrome (SS) and in NOD and NOD.scid mice express Fas and Fas ligand, and these cells die from apoptosis. To elucidate the intracellular molecular mechanisms responsible for this salivary gland epithelial cell apoptosis, expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x L, Bax) and caspase (caspases 3 and 8) was studied in young (ages 8-10 weeks) and old (ages 17-28 weeks) NOD and NOD.scid mice. Methods. Sections of frozen salivary gland tissue were obtained from NOD and NOD.scid mice and from the lip biopsy material of SS patients. Immunohisto-chemistry or Western blot analysis was performed to assess the apoptotic-associated proteins. Results. Levels of Bax and caspase 3 were elevated in the epithelial cells of glands from old NOD mice, but not in those from young NOD mice. In contrast, epithelial cells from both young and old NOD.scid mice exhibited strong expression of Bax and caspase 3. Western blot analysis showed that the activated form of caspase 3 was increased 2-5-fold in the glands from old NOD, old NOD.scid, and young NOD.scid mice compared with those from young NOD mice. Caspase 3 was also significantly elevated (P < 0.01) in SS patients whose focus scores were grade 3 or 4. In the SS patients' biopsy tissue and in the mouse glands, cells with fragmented DNA were positive for caspase 3. Conclusion. These results demonstrate that salivary gland epithelial cells in NOD and NOD.scid mice overexpress the proapoptotic molecules Bax and caspase 3. Bax could be the gene responsible for initiation of caspase activation, epithelial cell destruction, and lymphocyte glandular localization in SS.

Original languageEnglish (US)
Pages (from-to)693-702
Number of pages10
JournalArthritis and Rheumatism
Volume44
Issue number3
DOIs
StatePublished - 2001

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Caspase 3
Epithelial Cells
Salivary Glands
Inbred NOD Mouse
Caspases
Western Blotting
Apoptosis
Biopsy
Fas Ligand Protein
Caspase 8
Frozen Sections
Lip
Proteins
Lymphocytes
DNA
Genes

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

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Elevated proapoptotic bax and caspase 3 activation in the NOD.scid model of Sjögren's syndrome. / Masago, Reiji; Aiba-Masago, Sonomi; Talal, Norman; Zuluaga, Fabio Jimenez; Al-Hashimi, Ibtisam; Moody, Michael; Allen Lau, C.; Peck, Ammon B.; Brayer, Jason; Humphreys-Beher, Michael G.; Dang, Howard.

In: Arthritis and Rheumatism, Vol. 44, No. 3, 2001, p. 693-702.

Research output: Contribution to journalArticle

Masago, R, Aiba-Masago, S, Talal, N, Zuluaga, FJ, Al-Hashimi, I, Moody, M, Allen Lau, C, Peck, AB, Brayer, J, Humphreys-Beher, MG & Dang, H 2001, 'Elevated proapoptotic bax and caspase 3 activation in the NOD.scid model of Sjögren's syndrome', Arthritis and Rheumatism, vol. 44, no. 3, pp. 693-702. https://doi.org/10.1002/1529-0131(200103)44:3<693::AID-ANR119>3.0.CO;2-7
Masago, Reiji ; Aiba-Masago, Sonomi ; Talal, Norman ; Zuluaga, Fabio Jimenez ; Al-Hashimi, Ibtisam ; Moody, Michael ; Allen Lau, C. ; Peck, Ammon B. ; Brayer, Jason ; Humphreys-Beher, Michael G. ; Dang, Howard. / Elevated proapoptotic bax and caspase 3 activation in the NOD.scid model of Sjögren's syndrome. In: Arthritis and Rheumatism. 2001 ; Vol. 44, No. 3. pp. 693-702.
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abstract = "Objective. Salivary gland epithelial cells in patients with Sj{\"o}gren's syndrome (SS) and in NOD and NOD.scid mice express Fas and Fas ligand, and these cells die from apoptosis. To elucidate the intracellular molecular mechanisms responsible for this salivary gland epithelial cell apoptosis, expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x L, Bax) and caspase (caspases 3 and 8) was studied in young (ages 8-10 weeks) and old (ages 17-28 weeks) NOD and NOD.scid mice. Methods. Sections of frozen salivary gland tissue were obtained from NOD and NOD.scid mice and from the lip biopsy material of SS patients. Immunohisto-chemistry or Western blot analysis was performed to assess the apoptotic-associated proteins. Results. Levels of Bax and caspase 3 were elevated in the epithelial cells of glands from old NOD mice, but not in those from young NOD mice. In contrast, epithelial cells from both young and old NOD.scid mice exhibited strong expression of Bax and caspase 3. Western blot analysis showed that the activated form of caspase 3 was increased 2-5-fold in the glands from old NOD, old NOD.scid, and young NOD.scid mice compared with those from young NOD mice. Caspase 3 was also significantly elevated (P < 0.01) in SS patients whose focus scores were grade 3 or 4. In the SS patients' biopsy tissue and in the mouse glands, cells with fragmented DNA were positive for caspase 3. Conclusion. These results demonstrate that salivary gland epithelial cells in NOD and NOD.scid mice overexpress the proapoptotic molecules Bax and caspase 3. Bax could be the gene responsible for initiation of caspase activation, epithelial cell destruction, and lymphocyte glandular localization in SS.",
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T1 - Elevated proapoptotic bax and caspase 3 activation in the NOD.scid model of Sjögren's syndrome

AU - Masago, Reiji

AU - Aiba-Masago, Sonomi

AU - Talal, Norman

AU - Zuluaga, Fabio Jimenez

AU - Al-Hashimi, Ibtisam

AU - Moody, Michael

AU - Allen Lau, C.

AU - Peck, Ammon B.

AU - Brayer, Jason

AU - Humphreys-Beher, Michael G.

AU - Dang, Howard

PY - 2001

Y1 - 2001

N2 - Objective. Salivary gland epithelial cells in patients with Sjögren's syndrome (SS) and in NOD and NOD.scid mice express Fas and Fas ligand, and these cells die from apoptosis. To elucidate the intracellular molecular mechanisms responsible for this salivary gland epithelial cell apoptosis, expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x L, Bax) and caspase (caspases 3 and 8) was studied in young (ages 8-10 weeks) and old (ages 17-28 weeks) NOD and NOD.scid mice. Methods. Sections of frozen salivary gland tissue were obtained from NOD and NOD.scid mice and from the lip biopsy material of SS patients. Immunohisto-chemistry or Western blot analysis was performed to assess the apoptotic-associated proteins. Results. Levels of Bax and caspase 3 were elevated in the epithelial cells of glands from old NOD mice, but not in those from young NOD mice. In contrast, epithelial cells from both young and old NOD.scid mice exhibited strong expression of Bax and caspase 3. Western blot analysis showed that the activated form of caspase 3 was increased 2-5-fold in the glands from old NOD, old NOD.scid, and young NOD.scid mice compared with those from young NOD mice. Caspase 3 was also significantly elevated (P < 0.01) in SS patients whose focus scores were grade 3 or 4. In the SS patients' biopsy tissue and in the mouse glands, cells with fragmented DNA were positive for caspase 3. Conclusion. These results demonstrate that salivary gland epithelial cells in NOD and NOD.scid mice overexpress the proapoptotic molecules Bax and caspase 3. Bax could be the gene responsible for initiation of caspase activation, epithelial cell destruction, and lymphocyte glandular localization in SS.

AB - Objective. Salivary gland epithelial cells in patients with Sjögren's syndrome (SS) and in NOD and NOD.scid mice express Fas and Fas ligand, and these cells die from apoptosis. To elucidate the intracellular molecular mechanisms responsible for this salivary gland epithelial cell apoptosis, expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x L, Bax) and caspase (caspases 3 and 8) was studied in young (ages 8-10 weeks) and old (ages 17-28 weeks) NOD and NOD.scid mice. Methods. Sections of frozen salivary gland tissue were obtained from NOD and NOD.scid mice and from the lip biopsy material of SS patients. Immunohisto-chemistry or Western blot analysis was performed to assess the apoptotic-associated proteins. Results. Levels of Bax and caspase 3 were elevated in the epithelial cells of glands from old NOD mice, but not in those from young NOD mice. In contrast, epithelial cells from both young and old NOD.scid mice exhibited strong expression of Bax and caspase 3. Western blot analysis showed that the activated form of caspase 3 was increased 2-5-fold in the glands from old NOD, old NOD.scid, and young NOD.scid mice compared with those from young NOD mice. Caspase 3 was also significantly elevated (P < 0.01) in SS patients whose focus scores were grade 3 or 4. In the SS patients' biopsy tissue and in the mouse glands, cells with fragmented DNA were positive for caspase 3. Conclusion. These results demonstrate that salivary gland epithelial cells in NOD and NOD.scid mice overexpress the proapoptotic molecules Bax and caspase 3. Bax could be the gene responsible for initiation of caspase activation, epithelial cell destruction, and lymphocyte glandular localization in SS.

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