title: GOLPH3 Mediated Golgi Stress Response in Modulating N2A Cell Death upon Oxygen-Glucose Deprivation and Reoxygenation Injury.
abstract: Increasing evidence implicating that the organelle-dependent initiation of cell death merits further research. The evidence also implicates Golgi as a sensor and common downstream-effector of stress signals in cell death pathways, and it undergoes disassembly and fragmentation during apoptosis in several neurological disorders. It has also been reported that during apoptotic cell death, there is a cross talk between ER, mitochondria, and Golgi. Thus, we hypothesized that Golgi might trigger death signals during oxidative stress through its own machinery. The current study found that GOLPH3, an outer membrane protein of the Golgi complex, was significantly upregulated in N2A cells upon oxygen-glucose deprivation and reoxygenation (OGD/R), positioning from the compact perinuclear ribbon to dispersed vesicle-like structures throughout the cytoplasm. Additionally, elevated GOLPH3 promoted a stress-induced conversion of the LC3 subunit I to II and reactive oxygen species (ROS) production in long-term OGD/R groups. The collective data indicated that GOLPH3 not only acted as a sensor of Golgi stress for its prompt upregulation during oxidative stress but also as an initiator that triggered and propagated specific Golgi stress signals to downstream effectors. This affected ROS production and stress-related autophagy and finally controlled the entry into apoptosis. The data also supported the hypothesis that the Golgi apparatus could be an ideal target for stroke, neurodegenerative diseases, or cancer therapy through its own functional proteins.
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors: Ting
authors: T
authors: Li
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors: Hong
authors: H
authors: You
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors: Xiaoye
authors: X
authors: Mo
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors: Wenfang
authors: W
authors: He
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors: Xiangqi
authors: X
authors: Tang
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors: Zheng
authors: Z
authors: Jiang
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors: Shiyu
authors: S
authors: Chen
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China.
authors: Yang
authors: Y
authors: Chen
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China. lilisten2011@163.com.
authors: Jie
authors: J
authors: Zhang
authors: The Second Xiangya Hospital Central South University, Changsha, Hunan, China. huzhipingxy@gmail.com.
authors: Zhiping
authors: Z
authors: Hu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005947:Glucose / Q000172:deficiency*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010100:Oxygen / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D013997:Time Factors
chemical_list: C523967:GPP34 protein, mouse; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; D005947:Glucose; D010100:Oxygen
keywords: Apoptosis; Autophagy; ER stress; GOLPH3; Golgi stress response; Ischemia/reperfusion; Mitochondria; Oxidative stress; Oxygen-glucose deprivation and reoxygenation (OGD/R); Reactive oxygen species (ROS)
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