title: Effect of Phenylephrine Pretreatment on the Expressions of Aquaporin 5 and c-Jun N-Terminal Kinase in Irradiated Submandibular Gland.
abstract: Radiotherapy for malignant tumors of the head and neck commonly leads to radiation-induced sialadenitis as a result of radiation-induced salivary gland dysfunction. We demonstrated previously that phenylephrine could protect the irradiated submandibular gland against apoptosis, although the mechanism is unclear. In this study, we investigated the influence of phenylephrine pretreatment on the expressions of aquaporin 5 (AQP5) and c-Jun N-terminal kinase (JNK) that were presumed to have a role in radiation-induced salivary gland dysfunction. Rats pretreated with phenylephrine (5 mg/kg) were locally irradiated (20 Gy) in the head and neck region. The submandibular glands were removed on day 7 after irradiation. The expression of AQP5 and activation of JNK were measured by immunohistochemistry and Western blot. The localization of AQP5 at the apical and lateral plasma membrane of acinar cells was significantly reduced by irradiation, but markedly enhanced with phenylephrine pretreatment. The protein expression of AQP5 was decreased by 84.91% in irradiated glands, whereas it was fully recovered to the control level in phenylephrine-pretreated glands. Moreover, many acinar, ductal and granular convoluted tubular cells in the irradiated glands exhibited intense immunoreactivity for p-JNK, while in the phenylephrine-pretreated irradiated glands, only a few acinar cells exhibited very faint immunoreactivity for p-JNK. The protein expression level of p-JNK was increased by 41.65% in the irradiated alone glands, but was significantly decreased in the phenylephrine-pretreated irradiated glands. These results suggest that the protective mechanism of phenylephrine might be related to the improved expression of AQP5 and decreased activation of JNK. Pretreatment with phenylephrine in patients undergoing radiotherapy may provide a helpful strategy for suppression of radiation-induced sialadenitis.
authors.affiliation: a  Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Dalian 116622, P.R. China;
authors.forename: Lichi
authors.initials: L
authors.lastname: Han
authors.affiliation: a  Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Dalian 116622, P.R. China;
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: b  Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, P.R. China; and.
authors.forename: Fuyin
authors.initials: F
authors.lastname: Zhang
authors.affiliation: c  Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131.
authors.forename: Ke Jian
authors.initials: KJ
authors.lastname: Liu
authors.affiliation: a  Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Dalian 116622, P.R. China;
authors.forename: Bin
authors.initials: B
authors.lastname: Xiang
mesh_terms: D000818:Animals; D051402:Aquaporin 5 / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D016764:Cell Polarity / Q000187:drug effects / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D010656:Phenylephrine / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*
chemical_list: D051402:Aquaporin 5; D010750:Phosphoproteins; D011837:Radiation-Protective Agents; D010656:Phenylephrine; D048031:JNK Mitogen-Activated Protein Kinases