Signaling pathways involved in HSP32 induction by hyperbaric oxygen in rat spinal neurons.
Redox Biol
; 10: 108-118, 2016 12.
Article
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| MEDLINE
| ID: mdl-27721085
ABSTRACT
Spinal cord injury (SCI) is a debilitating disease, effective prevention measures are in desperate need. Our previous work found that hyperbaric oxygen (HBO) preconditioning significantly protected rats from SCI after stimulated diving, and in vitro study further testified that HBO protected primary cultured rat spinal neurons from oxidative insult and oxygen glucose deprivation injury via heat shock protein (HSP) 32 induction. In this study, underlying molecular mechanisms were further investigated. The results showed that a single exposure to HBO significantly increased intracellular levels of reactive oxygen species (ROS) and nitric oxide (NO) and activated MEK1/2, ERK1/2, p38 MAPK, CREB, Bach1 and Nrf2. The induction of HSP32 by HBO was significantly reversed by pretreatment neurons with ROS scavenger N-Acetyl-L-cysteine, p38 MAPK inhibitor or Nrf2 gene knockdown, enhanced by MEK1/2 inhibitors or gene knockdown but not by ERK1/2 inhibitor. CREB knockdown did not change the expression of HSP32 induced by HBO. N-Acetyl-L-cysteine significantly inhibited the activation of MEK1/2, ERK1/2, p38 MAPK, and Nrf2. Activation of Nrf2 was significantly inhibited by p38 MAPK inhibitor and the nuclear export of Bach1 was significantly enhanced by MEK1/2 inhibitor. The results demonstrated that HBO induces HSP32 expression through a ROS/p38 MAPK/Nrf2 pathway and the MEK1/2/Bach1 pathway contributes to negative regulation in the process. More importantly, as we know, this is the first study to delineate that ERK1/2 is not the only physiological substrates of MEK1/2.
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Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Terapias_biologicas
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Oxigenoterapia_hiperbrica
Asunto principal:
Médula Espinal
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Especies Reactivas de Oxígeno
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Hemo Oxigenasa (Desciclizante)
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Oxigenoterapia Hiperbárica
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Óxido Nítrico
Idioma:
En
Revista:
Redox Biol
Año:
2016
Tipo del documento:
Article