Exosomal secretion of death bullets: a new way of apoptotic escape?

Nina Trokovic1, Raimo Pöllänen, Pauliina Porola

  • 1Department of Medicine, Helsinki University Hospital, Helsinki, Finland.

Insights

Dihydrotestosterone (DHT) prevents apoptosis in salivary gland cells, while androgen deficiency accelerates it. Dehydroepiandrosterone (DHEA) treatment protected cells by converting to DHT, highlighting its therapeutic potential.

Area of Science:

  • Endocrinology and Cell Biology
  • Salivary Gland Physiology
  • Apoptosis and Cell Death Pathways

Background:

  • Estrogen deficiency (ovariectomy) induces apoptosis in mouse submandibular gland (SMG) serous epithelial cells.
  • This apoptosis is absent in estrogen-deficient males, suggesting a protective role for androgens.
  • Dihydrotestosterone (DHT) is hypothesized to protect SMG epithelial cells from apoptosis.

Purpose of the Study:

  • To investigate the antiapoptotic effect of DHT on human salivary gland (HSG) cells.
  • To examine the proapoptotic impact of androgen deficiency in mice.
  • To evaluate the protective effects of dehydroepiandrosterone (DHEA) in an androgen-deficient model.

Main Methods:

  • DHT's effect on TNF-α/cycloheximide-induced apoptosis in HSG cells.
  • Studied apoptosis in orchiectomized (ORX) androgen-knockout (ARKO) and wild-type (WT) mice.
  • Assessed cell health via staining (AB-PAS, amylase), TEM, and apoptosis markers (caspase-8/3, TUNEL assay).

Main Results:

  • DHT demonstrated antiapoptotic effects on HSG cells.
  • Androgen deficiency in mice led to caspase activation and secretion in exosome-like particles, impacting cell morphology and secretory function.
  • DHEA treatment normalized cell morphology and function in WT ORX mice, but not ARKO ORX mice, suggesting intracrine conversion to DHT.

Conclusions:

  • DHT protects salivary gland epithelial cells against apoptosis.
  • Androgen deficiency promotes apoptosis and alters salivary gland cell function.
  • DHEA exhibits protective effects, likely through intracrine conversion to DHT, indicating potential therapeutic applications.

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