17β-Estradiol up-regulates Nrf2 via PI3K/AKT and estrogen receptor signaling pathways to suppress light-induced degeneration in rat retina

C, Zhu; Wang, S.; Wang, B.; Du, Fuxin; Hu, Congcong; Li, H.; Feng, Yan; Zhu, Rui; Mo, Mingshu; Cao, Yang; Li, A.; Yu, Xiaorui

doi:10.1016/j.neuroscience.2015.07.057

Cited by 59 publications

(45 citation statements)

References 43 publications

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“…The phosphatidylinositol 3-kinase-Akt (PI3K/AKT) signalling pathway, which is involved in the control of cell survival, differentiation, growth and apoptosis, is activated when retinal layers are exposed to oxidative stress. In particular, it has been found that PI3K/ AKT can exert retinal protection against light-or hydrogen peroxide-induced apoptosis by modulation of mitochondrial apoptosis signalling (Zhu et al 2015). The results of our study would be in agreement with previous observations.…”

Section: Discussionsupporting

confidence: 94%

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The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes

Cillà

Vezzola

Farruggio

et al. 2018

Acta Ophthalmologica

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Purpose Subthreshold micropulse laser (SMPL) has been increasingly used for the treatment of different retinal and choroidal macular disorders. However, the exact mechanisms of action have not yet been clearly defined. Therefore, we aimed to examine the role of SMPL treatment in the modulation of oxidant/antioxidant systems, apoptosis and autophagy in the mice eyes. Methods A specific laser contact lens for retina was positioned on the cornea of 40 mice (20 young and 20 old) in order to focus the laser on the eye fundus for SMPL treatment. Within 6 months, 20 animals received one treatment only, whereas the others were treated three times. Eye specimens underwent histological analysis and were used for thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) quantification, as well as for the superoxide dismutase 1 (SOD1) and the selenoprotein thioredoxin reductase 1 (TrxR1) expression evaluation. Western blot was performed for nitric oxide synthase (NOS) subtypes detection and to examine changes in apoptotic/autophagy proteins expression. Results SMPL treatment reduced TBARS and increased GSH and SOD1 in the mice eyes. It also reduced cytochrome c, caspase 3 expression and activity and cleaved caspase 9, and increased Beclin 1, p62 and LC3β. The effects were more relevant in the elderly animals. Conclusion Our results showed that SMPL therapy restored the oxidant/antioxidant balance within retinal layers and modulated programmed forms of cell death. Further studies may confirm these data and could evaluate their relevance in clinical practice.

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Section: Discussionsupporting

confidence: 94%

“…In particular, it has been found that PI3K/AKT can exert retinal protection against light‐ or hydrogen peroxide‐induced apoptosis by modulation of mitochondrial apoptosis signalling (Zhu et al. ). The results of our study would be in agreement with previous observations.…”

Section: Discussionmentioning

confidence: 99%

The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes

Cillà

Vezzola

Farruggio

et al. 2018

Acta Ophthalmologica

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“…The Akt pathway has been shown to be involved with various physiological and pathological process, including tumorigenesis and hypoxia (Di et al, 2015; Liu et al, 2015; Zhu et al, 2015). In RGCs, cobalt induced a significant decrease in the level of phosphorylated Akt without altering the total Akt expression level (Figures 3A,B).…”

Section: Resultsmentioning

confidence: 99%

Baclofen Protects Primary Rat Retinal Ganglion Cells from Chemical Hypoxia-Induced Apoptosis Through the Akt and PERK Pathways

et al. 2016

Front. Cell. Neurosci.

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Retinal ganglion cells (RGCs) consume large quantities of energy to convert light information into a neuronal signal, which makes them highly susceptible to hypoxic injury. This study aimed to investigate the potential protection by baclofen, a GABAB receptor agonist of RGCs against hypoxia-induced apoptosis. Cobalt chloride (CoCl2) was applied to mimic hypoxia. Primary rat RGCs were subjected to CoCl2 with or without baclofen treatment, and RNA interference techniques were used to knock down the GABAB2 gene in the primary RGCs. The viability and apoptosis of RGCs were assessed using cell viability and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays, Hoechst staining, and flow cytometry. The expression of cleaved caspase-3, bcl-2, bax, Akt, phospho-Akt, protein kinase RNA (PKR)-like ER kinase (PERK), phospho-PERK, eIF2α, phospho-eIF2α, ATF-4 and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured using western blotting. GABAB2 mRNA expression was determined using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Our study revealed that CoCl2 significantly induced RGC apoptosis and that baclofen reversed these effects. CoCl2-induced reduction of Akt activity was also reversed by baclofen. Baclofen prevented the activation of the PERK pathway and the increase in CHOP expression induced by CoCl2. Knockdown of GABAB2 and the inactivation of the Akt pathway by inhibitors reduced the protective effect of baclofen on CoCl2-treated RGCs. Taken together, these results demonstrate that baclofen protects RGCs from CoCl2-induced apoptosis by increasing Akt activity and by suppressing the PERK pathway and CHOP activation.

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“…Female hormones may increase the sensitivity for developing chronic pain or decrease the nociception of pain, dependent upon the menses cycle (Prusator and Meerveld, 2016). In addition, it appears that the female brain might be more resistant to the inflammatory process than the male brain via Nrf2 upregulation by sex steroid hormones, such as 17β-estradiol (Zhu et al, 2015). Sex hormones were not investigated in this experiment; hence it remains to be determined how they might affect inflammatory processes under normal mood conditions.…”

Section: Discussionmentioning

confidence: 99%

BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia

López-Granero

Santos

Ferrer

et al. 2017

Psychoneuroendocrinology

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Depression and anxiety are the most common psychiatric disorders, representing a major public health concern. Dysregulation of oxidative and inflammatory systems may be associated with psychiatric disorders, such as depression and anxiety. Due to the need to find appropriate animal models to the understanding of such disorders, we queried whether 2 BXD recombinant inbred (RI) mice strains (BXD21/TyJ RI and BXD84/RwwJ RI mice) and C57BL/6 wild-type mice show differential performance in depression and anxiety related behaviors and biomarkers. Specifically, we assessed forced swim, elevated plus maze, social preference and Von Frey tests at 3-4 months-of-age, as well as activation of cytokines and antioxidant mRNA levels in the cortex at 7 months-of-age. We report that (1) the BXD84/RwwJ RI strain exhibits anxiety disorder and social avoidance-like behavior (2) BXD21/TyJ RI strain show a resistance to depression illness, and (3) sex-dependent cytokine profiles and allodynia with elevated inflammatory activity were inherent to male BXD21/TyJ RI mice. In conclusion, we provide novel data in favor of the use of BXD recombinant inbred mice to further understand anxiety and depression disorders.

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17β-Estradiol up-regulates Nrf2 via PI3K/AKT and estrogen receptor signaling pathways to suppress light-induced degeneration in rat retina

Cited by 59 publications

References 43 publications

The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes

The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes

Baclofen Protects Primary Rat Retinal Ganglion Cells from Chemical Hypoxia-Induced Apoptosis Through the Akt and PERK Pathways

BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia

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