Radioprotective effect of heat shock protein 25 on submandibular glands of rats

Am J Pathol. 2006 Nov;169(5):1601-11. doi: 10.2353/ajpath.2006.060327.


Irradiation (IR) is a fundamental treatment modality for head and neck malignancies. However, a significant drawback of IR treatment is irreversible damage of salivary gland in the IR field. In the present study, we investigated whether heat shock protein (HSP) 25 could be used as a radioprotective molecule for radiation-induced salivary gland damage in rats. HSP25 as well as inducible HSP70 (HSP70i) that were delivered to the salivary gland via an adenoviral vector significantly ameliorated radiation-induced salivary fluid loss. Radiation-induced apoptosis, caspase-3 activation, and poly(ADP-ribose) polymerase cleavage in acinar cells, granular convoluted cells, and intercalated ductal cells were also inhibited by HSP25 or HSP70i transfer. The alteration of salivary contents, including amylase, protein, Ca+, Cl-, and Na+, was also attenuated by HSP25 transfer. Histological analysis revealed almost no radiation-induced damage in salivary gland when HSP25 was transferred. Aquaporin 5 expression in salivary gland was inhibited by radiation; and HSP25 transfer to salivary gland prevented this alteration. The protective effect of HSP70i on radiation-induced salivary gland damage was less or delayed than that of HSP25. These results indicate that HSP25 is a good candidate molecule to protect salivary gland from the toxicity of IR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Aquaporin 5 / metabolism
  • Body Weight / drug effects
  • Body Weight / radiation effects
  • Caspase 3 / metabolism
  • Genetic Vectors
  • HSP70 Heat-Shock Proteins / metabolism
  • Heat-Shock Proteins / metabolism*
  • Male
  • Mice
  • Molecular Chaperones
  • Neoplasm Proteins / metabolism*
  • Organ Size / drug effects
  • Organ Size / radiation effects
  • Pilocarpine / pharmacology
  • Poly(ADP-ribose) Polymerases / metabolism
  • Protein Transport / drug effects
  • Protein Transport / radiation effects
  • Radiation, Ionizing
  • Radiation-Protective Agents / metabolism*
  • Rats
  • Rats, Wistar
  • Saliva / drug effects
  • Saliva / radiation effects
  • Submandibular Gland / cytology
  • Submandibular Gland / metabolism*
  • Submandibular Gland / pathology
  • Submandibular Gland / radiation effects*


  • Aquaporin 5
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Hsbp1 protein, mouse
  • Molecular Chaperones
  • Neoplasm Proteins
  • Radiation-Protective Agents
  • Pilocarpine
  • Poly(ADP-ribose) Polymerases
  • Caspase 3