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Novel role for RbAp48 in tissue-specific, estrogen deficiency-dependent apoptosis in the exocrine glands

Naozumi Ishimaru1, Rieko Arakaki, Fumie Omotehara

  • 1Department of Oral Molecular Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3 Kuramotocho, Tokushima 770-8504, Japan.

Molecular and Cellular Biology
|April 4, 2006
PubMed

Insights

Estrogen deficiency causes RbAp48 overexpression, leading to p53-mediated apoptosis in exocrine glands. This mechanism may explain autoimmune exocrinopathy risk in postmenopausal women.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Immunology

Background:

  • Tissue-specific apoptosis in exocrine glands is implicated in autoimmune exocrinopathy.
  • The precise molecular mechanisms driving this apoptosis in estrogen deficiency remain unclear.

Purpose of the Study:

  • To elucidate the molecular pathway of tissue-specific apoptosis in estrogen-deficient exocrine glands.
  • To investigate the role of RbAp48 in estrogen deficiency-induced apoptosis.

Main Methods:

  • Utilized RbAp48-inducible transfectants and small interfering RNA (siRNA) to modulate RbAp48 expression.
  • Examined p53 phosphorylation (Ser9) and alpha-fodrin cleavage as markers of apoptosis.
  • Compared apoptosis in ovariectomized (OVX) wild-type mice with OVX estrogen receptor alpha(-/-), p53(-/-), and E2F-1(-/-) mice.

Main Results:

  • RbAp48 overexpression triggered p53-mediated apoptosis in exocrine glands, evidenced by p53 phosphorylation and alpha-fodrin cleavage.
  • siRNA-mediated reduction of RbAp48 inhibited this apoptosis.
  • Elevated RbAp48 expression and apoptosis were observed in OVX C57BL/6 mice but not in OVX mice lacking estrogen receptor alpha, p53, or E2F-1.
  • Transgenic RbAp48 expression induced apoptosis specifically in exocrine glands.

Conclusions:

  • Estrogen deficiency induces apoptosis in exocrine gland cells via RbAp48 overexpression and p53 activation.
  • This pathway highlights a potential gender-based risk for autoimmune exocrinopathy in postmenopausal women.

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