Chronic social isolation induces NF-kappa B activation and upregulation of iNOS protein expression in rat prefrontal cortex
Апстракт
Exposure of an organism to stress, results in oxidative stress and increased nitric oxide (NO) production in the brain. The role of the processes caused by chronic stress in the prefrontal cortex has not been fully investigated. Considering that chronic stress increases NO production by the enzyme nitric oxide synthase (NOS), we examined the cytosolic neuronal (nNOS) or inducible (iNOS) protein levels in the prefrontal cortex of rats exposed to 21 d of chronic social isolation stress, an animal model of depression, alone or in combination with 2 h of acute immobilization or cold (4 degrees C) stress (combined stress). Antioxidative status via cytosolic CuZnSOD and mitochondrial MnSOD activity, cytosolic redox status via reduced glutathione (GSH) concentration were determined. Furthermore, cytosolic inducible heat shock protein 70 (Hsp70i), cytosolic/nuclear distributions of NF-kappa B and serum corticosterone (CORT) were also investigated to elucidate the possible mechanism involved in... the cellular NOS pathway. Our results showed that both acute stressors led to increases of CORT and nNOS protein while iNOS protein expression was unaffected. In contrast to the acute stress, chronic social isolation compromised hypothalamic-pituitary-adrenal axis functioning such that the normal stress response was impaired following subsequent acute stressors. Downregulated redox GSH status as well as decreased activity of CuZnSOD and MnSOD suggests the existence of oxidative stress which remained as such following combined stressors. Changes in redox-status associated with decreased Hsp70i protein expression enabled NF-kappa B translocation into the nucleus, causing increased cytosolic nNOS and iNOS protein expression. Results suggest that NOS signaling pathway plays a differential role between acute and chronic stress whereby state of oxidative/nitrosative stress after chronic social isolation is caused, at least in part, by NF-kappa B activation and increased iNOS protein expression. (C) 2013 Elsevier Ltd. All rights reserved.
Кључне речи:
Chronic social isolation / Prefrontal cortex / Oxidative stress / Nitric oxide synthases / Hsp70iИзвор:
Neurochemistry International, 2013, 63, 3, 172-179Финансирање / пројекти:
DOI: 10.1016/j.neuint.2013.06.002
ISSN: 0197-0186
PubMed: 23770205
WoS: 000323590300007
Scopus: 2-s2.0-84884846291
Институција/група
VinčaTY - JOUR AU - Martinović, Jelena AU - Filipović, Dragana PY - 2013 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5645 AB - Exposure of an organism to stress, results in oxidative stress and increased nitric oxide (NO) production in the brain. The role of the processes caused by chronic stress in the prefrontal cortex has not been fully investigated. Considering that chronic stress increases NO production by the enzyme nitric oxide synthase (NOS), we examined the cytosolic neuronal (nNOS) or inducible (iNOS) protein levels in the prefrontal cortex of rats exposed to 21 d of chronic social isolation stress, an animal model of depression, alone or in combination with 2 h of acute immobilization or cold (4 degrees C) stress (combined stress). Antioxidative status via cytosolic CuZnSOD and mitochondrial MnSOD activity, cytosolic redox status via reduced glutathione (GSH) concentration were determined. Furthermore, cytosolic inducible heat shock protein 70 (Hsp70i), cytosolic/nuclear distributions of NF-kappa B and serum corticosterone (CORT) were also investigated to elucidate the possible mechanism involved in the cellular NOS pathway. Our results showed that both acute stressors led to increases of CORT and nNOS protein while iNOS protein expression was unaffected. In contrast to the acute stress, chronic social isolation compromised hypothalamic-pituitary-adrenal axis functioning such that the normal stress response was impaired following subsequent acute stressors. Downregulated redox GSH status as well as decreased activity of CuZnSOD and MnSOD suggests the existence of oxidative stress which remained as such following combined stressors. Changes in redox-status associated with decreased Hsp70i protein expression enabled NF-kappa B translocation into the nucleus, causing increased cytosolic nNOS and iNOS protein expression. Results suggest that NOS signaling pathway plays a differential role between acute and chronic stress whereby state of oxidative/nitrosative stress after chronic social isolation is caused, at least in part, by NF-kappa B activation and increased iNOS protein expression. (C) 2013 Elsevier Ltd. All rights reserved. T2 - Neurochemistry International T1 - Chronic social isolation induces NF-kappa B activation and upregulation of iNOS protein expression in rat prefrontal cortex VL - 63 IS - 3 SP - 172 EP - 179 DO - 10.1016/j.neuint.2013.06.002 ER -
@article{ author = "Martinović, Jelena and Filipović, Dragana", year = "2013", abstract = "Exposure of an organism to stress, results in oxidative stress and increased nitric oxide (NO) production in the brain. The role of the processes caused by chronic stress in the prefrontal cortex has not been fully investigated. Considering that chronic stress increases NO production by the enzyme nitric oxide synthase (NOS), we examined the cytosolic neuronal (nNOS) or inducible (iNOS) protein levels in the prefrontal cortex of rats exposed to 21 d of chronic social isolation stress, an animal model of depression, alone or in combination with 2 h of acute immobilization or cold (4 degrees C) stress (combined stress). Antioxidative status via cytosolic CuZnSOD and mitochondrial MnSOD activity, cytosolic redox status via reduced glutathione (GSH) concentration were determined. Furthermore, cytosolic inducible heat shock protein 70 (Hsp70i), cytosolic/nuclear distributions of NF-kappa B and serum corticosterone (CORT) were also investigated to elucidate the possible mechanism involved in the cellular NOS pathway. Our results showed that both acute stressors led to increases of CORT and nNOS protein while iNOS protein expression was unaffected. In contrast to the acute stress, chronic social isolation compromised hypothalamic-pituitary-adrenal axis functioning such that the normal stress response was impaired following subsequent acute stressors. Downregulated redox GSH status as well as decreased activity of CuZnSOD and MnSOD suggests the existence of oxidative stress which remained as such following combined stressors. Changes in redox-status associated with decreased Hsp70i protein expression enabled NF-kappa B translocation into the nucleus, causing increased cytosolic nNOS and iNOS protein expression. Results suggest that NOS signaling pathway plays a differential role between acute and chronic stress whereby state of oxidative/nitrosative stress after chronic social isolation is caused, at least in part, by NF-kappa B activation and increased iNOS protein expression. (C) 2013 Elsevier Ltd. All rights reserved.", journal = "Neurochemistry International", title = "Chronic social isolation induces NF-kappa B activation and upregulation of iNOS protein expression in rat prefrontal cortex", volume = "63", number = "3", pages = "172-179", doi = "10.1016/j.neuint.2013.06.002" }
Martinović, J.,& Filipović, D.. (2013). Chronic social isolation induces NF-kappa B activation and upregulation of iNOS protein expression in rat prefrontal cortex. in Neurochemistry International, 63(3), 172-179. https://doi.org/10.1016/j.neuint.2013.06.002
Martinović J, Filipović D. Chronic social isolation induces NF-kappa B activation and upregulation of iNOS protein expression in rat prefrontal cortex. in Neurochemistry International. 2013;63(3):172-179. doi:10.1016/j.neuint.2013.06.002 .
Martinović, Jelena, Filipović, Dragana, "Chronic social isolation induces NF-kappa B activation and upregulation of iNOS protein expression in rat prefrontal cortex" in Neurochemistry International, 63, no. 3 (2013):172-179, https://doi.org/10.1016/j.neuint.2013.06.002 . .