PMID- 25891649 OWN - NLM STAT- MEDLINE DCOM- 20160706 LR - 20181113 IS - 1557-9042 (Electronic) IS - 0897-7151 (Print) IS - 0897-7151 (Linking) VI - 32 IP - 19 DP - 2015 Oct 1 TI - Chaperone-Mediated Autophagy after Traumatic Brain Injury. PG - 1449-57 LID - 10.1089/neu.2014.3694 [doi] AB - Chaperone-mediated autophagy (CMA) and the ubiquitin-proteasomal system (UPS) are two major protein degradation systems responsible for maintaining cellular homeostasis, but how these two systems are regulated after traumatic brain injury (TBI) remains unknown. TBI produces primary mechanical damage that must be repaired to maintain neuronal homeostasis. The level of lysosomal-associated membrane protein type 2A (LAMP2A) is the hallmark of CMA activity. The level of polyubiquitinated proteins (ubi-proteins) reflects UPS activity. This study utilized a moderate fluid percussion injury model in rats to investigate the changes in CMA and the UPS after TBI. Induction of CMA was manifested by significant upregulation of LAMP2A and secondary lysosomes during the periods of 1-15 days of recovery after TBI. In comparison, the levels of ubi-proteins were increased only moderately after TBI. The increases in the levels of LAMP2A and 70 kDa heat-shock protein for CMA after TBI were seen mainly in the secondary lysosome-containing fractions. Confocal and electron microscopy further showed that increased LAMP2A or lysosomes were found mainly in neurons and proliferated microglia. Because CMA and the UPS are two major routes for elimination of different types of cellular aberrant proteins, the consecutive activation of these two pathways may serve as a protective mechanism for maintaining cellular homeostasis after TBI. FAU - Park, Yujung AU - Park Y AD - 1 Neurochemistry Laboratory of Brain Injury, Shock Trauma and Anesthesiology Research Center; University of Maryland School of Medicine , Baltimore, Maryland. FAU - Liu, Chunli AU - Liu C AD - 1 Neurochemistry Laboratory of Brain Injury, Shock Trauma and Anesthesiology Research Center; University of Maryland School of Medicine , Baltimore, Maryland. FAU - Luo, Tianfei AU - Luo T AD - 1 Neurochemistry Laboratory of Brain Injury, Shock Trauma and Anesthesiology Research Center; University of Maryland School of Medicine , Baltimore, Maryland. FAU - Dietrich, W Dalton AU - Dietrich WD AD - 2 Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami School of Medicine , Miami, Florida. FAU - Bramlett, Helen AU - Bramlett H AD - 2 Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami School of Medicine , Miami, Florida. FAU - Hu, Bingren AU - Hu B AD - 1 Neurochemistry Laboratory of Brain Injury, Shock Trauma and Anesthesiology Research Center; University of Maryland School of Medicine , Baltimore, Maryland. LA - eng GR - R56 NS036810/NS/NINDS NIH HHS/United States GR - R01 NS040407/NS/NINDS NIH HHS/United States GR - NS030291/NS/NINDS NIH HHS/United States GR - R29 NS036810/NS/NINDS NIH HHS/United States GR - R01 NS036810/NS/NINDS NIH HHS/United States GR - I01 BX001696/BX/BLRD VA/United States GR - NS040407/NS/NINDS NIH HHS/United States GR - P50 NS030291/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20150630 PL - United States TA - J Neurotrauma JT - Journal of neurotrauma JID - 8811626 RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Lysosomal-Associated Membrane Protein 2) RN - 0 (Molecular Chaperones) RN - 0 (Ubiquitins) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) SB - IM MH - Animals MH - *Autophagy MH - Brain Injuries/*pathology MH - HSP70 Heat-Shock Proteins/metabolism MH - Homeostasis MH - Lysosomal-Associated Membrane Protein 2/metabolism MH - Lysosomes/metabolism MH - Male MH - Microglia/pathology MH - *Molecular Chaperones MH - Neurons/pathology MH - Proteasome Endopeptidase Complex MH - Rats MH - Rats, Sprague-Dawley MH - Signal Transduction MH - Ubiquitins/metabolism MH - Up-Regulation PMC - PMC4589263 OTO - NOTNLM OT - HSC70 OT - HSP70 OT - Iba-1 OT - LAMP2 OT - chaperone-mediated autophagy OT - lysosome OT - traumatic brain injury OT - ubiquitin EDAT- 2015/04/22 06:00 MHDA- 2016/07/07 06:00 PMCR- 2016/10/01 CRDT- 2015/04/21 06:00 PHST- 2015/04/21 06:00 [entrez] PHST- 2015/04/22 06:00 [pubmed] PHST- 2016/07/07 06:00 [medline] PHST- 2016/10/01 00:00 [pmc-release] AID - 10.1089/neu.2014.3694 [pii] AID - 10.1089/neu.2014.3694 [doi] PST - ppublish SO - J Neurotrauma. 2015 Oct 1;32(19):1449-57. doi: 10.1089/neu.2014.3694. Epub 2015 Jun 30.