title: Associations between autophagy, the ubiquitin-proteasome system and endoplasmic reticulum stress in hypoxia-deoxygenation or ischemia-reperfusion.
abstract: The activation of autophagy has been demonstrated to exert protective roles during hypoxia-reoxygenation (H/R)-induced brain injuries. This study aimed to investigate whether and how preconditioning with a proteasome inhibitor (MG-132), a proteasome promoter (Adriamycin, ADM), an autophagy inhibitor (3-methyladenine, 3-MA) and an autophagy promoter (Rapamycin, Rap) affected endoplasmic reticulum stress (ERS), the ubiquitin-proteasome system (UPS), autophagy, inflammation and apoptosis. Ubiquitin protein and 26S proteasome activity levels were decreased by MG-132 pretreatment but increased by ADM pretreatment at 2h, 4h and 6h following H/R treatment. MG-132 pretreatment led to the increased expression of autophagy-related genes, ER stress-associated genes and IκB but decreased the expression levels of NF-κB and caspase-3. ADM pretreatment led to the decreased expression of autophagy-related genes, ERS-associated genes and IκB but increased the expression of NF-κB and caspase-3. Pretreatment with 3-MA reduced the expression of autophagy-related genes, autophagy and UPS co-related genes, as well as apoptosis-related although the latter was increased by Rap pretreatment at 2h, 4h and 6h following H/R treatment. In vivo, pretreatment of rats with ADM, MG-132, 3-MA or Rap followed by ischemia-reperfusion (I/R) treatment resulted in similar changes. Proteasome inhibition preconditioning strengthened autophagy and ER stress but decreased apoptosis and inflammation. Autophagy promotion preconditioning exhibited similar changes. The combination of a proteasome inhibitor and an autophagy promoter might represent a new possible therapy to treat H/R or I/R injury-related diseases.
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Tao
authors: T
authors: Fan
authors: Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Zhixin
authors: Z
authors: Huang
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Lei
authors: L
authors: Chen
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Boyou
authors: B
authors: Zhang
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Yao
authors: Y
authors: Xu
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Shize
authors: S
authors: Pan
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Zhangfan
authors: Z
authors: Mao
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
authors: Hao
authors: H
authors: Hu
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China. Electronic address: szgqing@126.com.
authors: Qing
authors: Q
authors: Geng
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology*; D020123:Sirolimus / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D007976:Leupeptins; D016328:NF-kappa B; D025801:Ubiquitin; C025946:3-methyladenine; D004317:Doxorubicin; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; C545556:HDAC6 protein, rat; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases; D000225:Adenine; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D010100:Oxygen; D020123:Sirolimus
keywords: 3-MA (PubChem CID: 1673); Adriamycin (PubChem CID: 31703); Alveolar macrophage; Autophagy; Endoplasmic reticulum stress; Hypoxia-reoxygenation injury; Ischemia-reperfusion injury; MG-132 (PubChem CID: 462382); Proteasome; Rapamycin (PubChem CID: 5284616)