PMID- 20890458 OWN - NLM STAT- MEDLINE DCOM- 20110623 LR - 20211203 IS - 2041-4889 (Electronic) VI - 1 IP - 1 DP - 2010 TI - Activation of mTOR coincides with autophagy during ligation-induced atrophy in the rat submandibular gland. PG - e14 LID - 10.1038/cddis.2009.12 [doi] AB - Salivary gland atrophy is a common consequence of pathology, including Sjogren's syndrome, irradiation therapy and obstructive sialadenitis. During severe atrophy of the rat submandibular gland caused by excretory duct ligation, the majority of acinar cells disappear through apoptosis, whereas ductal cells proliferate and dedifferentiate; yet, the gland can survive in the atrophic state almost indefinitely, with an ability to fully recover if deligated. The control mechanisms governing these observations are not well understood. We report that ~10% of acinar cells survive in ligation-induced atrophy. Microarray and quantitative real-time PCR analysis of ligated glands indicated sustained transcription of acinar cell-specific genes, whereas ductal-specific genes were reduced to background levels. After 3 days of ligation, activation of the mammalian target of rapamycin (mTOR) pathway and autophagy occurred as shown by phosphorylation of 4E-BP1 and expression of autophagy-related proteins. These results suggest that activation of mTOR and the autophagosomal pathway are important mechanisms that may help to preserve acinar cells during atrophy of salivary glands after injury. FAU - Silver, N AU - Silver N AD - King's College London, Dental Institute, London, UK. FAU - Proctor, G B AU - Proctor GB FAU - Arno, M AU - Arno M FAU - Carpenter, G H AU - Carpenter GH LA - eng GR - Wellcome Trust/United Kingdom GR - 079066/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Aqp5 protein, rat) RN - 0 (Aquaporin 5) RN - 0 (Carrier Proteins) RN - 0 (Eif4ebp1 protein, rat) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (LOC100363344) RN - 0 (Phosphoproteins) RN - 0 (Salivary Proteins and Peptides) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Aquaporin 5/metabolism MH - Atrophy MH - *Autophagy MH - Carrier Proteins/metabolism MH - Gene Expression Regulation MH - Intracellular Signaling Peptides and Proteins MH - Ligation MH - Male MH - Phosphoproteins/metabolism MH - Rats MH - Rats, Wistar MH - Salivary Proteins and Peptides/metabolism MH - Signal Transduction MH - Submandibular Gland/cytology/*metabolism/*pathology MH - TOR Serine-Threonine Kinases/*metabolism PMC - PMC2948542 MID - UKMS30070 OTO - NOTNLM OT - atrophy OT - autophagy OT - mTOR OT - submandibular gland EDAT- 2010/10/05 06:00 MHDA- 2011/06/24 06:00 PMCR- 2010/01/01 CRDT- 2010/10/05 06:00 PHST- 2010/10/05 06:00 [entrez] PHST- 2010/10/05 06:00 [pubmed] PHST- 2011/06/24 06:00 [medline] PHST- 2010/01/01 00:00 [pmc-release] AID - cddis200912 [pii] AID - 10.1038/cddis.2009.12 [doi] PST - ppublish SO - Cell Death Dis. 2010;1(1):e14. doi: 10.1038/cddis.2009.12.