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Cell Death Dis ; 5: e1146, 2014 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-24675464

RESUMO

Salivary gland atrophy is a frequent consequence of head and neck cancer irradiation therapy but can potentially be regulated through the mammalian target of rapamycin (mTOR). Excretory duct ligation of the mouse submandibular gland provokes severe glandular atrophy causing activation of mTOR. This study aims to discover the effects of blocking mTOR signaling in ligation-induced atrophic salivary glands. Following 1 week of unilateral submandibular excretory duct ligation: gland weights were significantly reduced, 4E-BP1 and S6rp were activated, and tissue morphology revealed typical signs of atrophy. However, 3 days following ligation with rapamycin treatment, a selective mTOR inhibitor, gland weights were maintained, 4E-BP1 and S6rp phosphorylation was inhibited, and there were morphological signs of recovery from atrophy. However, following 5 and 7 days of ligation and rapamycin treatment, glands expressed active mTOR and showed signs of considerable atrophy. This evidence suggests that inhibition of mTOR by rapamycin delays ligation-induced atrophy of salivary glands.


Assuntos
Ductos Salivares/patologia , Ductos Salivares/cirurgia , Sirolimo/farmacologia , Células Acinares/efeitos dos fármacos , Células Acinares/metabolismo , Células Acinares/patologia , Animais , Atrofia , Feminino , Immunoblotting , Ligadura , Camundongos Endogâmicos ICR , Tamanho do Órgão/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Proteína S6 Ribossômica/metabolismo , Ductos Salivares/efeitos dos fármacos , Coloração e Rotulagem , Glândula Submandibular/efeitos dos fármacos , Glândula Submandibular/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Fatores de Tempo
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