Glucocorticoid-Induced Leucine Zipper Protects the Retina From Light-Induced Retinal Degeneration by Inducing Bcl-xL in Rats

Gu, Ruiping; Tang, Wenyi; Lei, Boya; Ding, Xinyi; Cheng, Jian; Xu, Gezhi

doi:10.1167/iovs.17-22116

Cited by 19 publications

(16 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data concerning the role of intrinsic mitochondria-driven apoptotic pathways as well as those of Gu et al show that light-induced retinal damage particularly stresses mitochondria, leading to cytochrome c release into the cytosol triggering apoptosis [37]. Here, we demonstrate for the first time a decreased Caspase-9 expression in mitochondria-rich IS, suggesting reduced mitochondria related apoptosis of RL/NIRL stimulated photoreceptors.…”

Section: Discussionsupporting

confidence: 75%

Photobiomodulation Mediates Neuroprotection against Blue Light Induced Retinal Photoreceptor Degeneration

Heinig

Schumann

Calzia

et al. 2020

IJMS

View full text Add to dashboard Cite

Potent neuroprotective effects of photobiomodulation with 670 nm red light (RL) have been demonstrated in several models of retinal disease. RL improves mitochondrial metabolism, reduces retinal inflammation and oxidative cell stress, showing its ability to enhance visual function. However, the current knowledge is limited to the main hypothesis that the respiratory chain complex IV, cytochrome c oxidase, serves as the primary target of RL. Here, we demonstrate a comprehensive cellular, molecular, and functional characterization of neuroprotective effects of 670 nm RL and 810 nm near-infrared light (NIRL) on blue light damaged murine primary photoreceptors. We show that respiratory chain complexes I and II are additional PBM targets, besides complex IV, leading to enhanced mitochondrial energy metabolism. Accordingly, our study identified mitochondria related RL- and NIRL-triggered defense mechanisms promoting photoreceptor neuroprotection. The observed improvement of mitochondrial and extramitochondrial respiration in both inner and outer segments is linked with reduced oxidative stress including its cellular consequences and reduced mitochondria-induced apoptosis. Analysis of regulatory mechanisms using gene expression analysis identified upregulation α-crystallins that indicate enhanced production of proteins with protective functions that point to the rescued mitochondrial function. The results support the hypothesis that energy metabolism is a major target for retinal light therapy.

show abstract

Section: Discussionsupporting

confidence: 75%

Photobiomodulation Mediates Neuroprotection against Blue Light Induced Retinal Photoreceptor Degeneration

Heinig

Schumann

Calzia

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…TSC22D3, identified as a glucocorticoid‐transactivated gene that functions as a transcriptional regulator, is known to promote the anti‐inflammatory, immunosuppressive, and anti‐proliferative actions of glucocorticoids in various cells . Overexpression of retinal TSC22D3 protected retinal neurons from light‐induced degeneration and lipopolysaccharide‐induced inflammation . TSC22D3 mainly exerts its effects by homo‐ or hetero‐dimerization with specific partner proteins, including transcription factors such as AP‐1, Raf‐1 and Ras, and regulates the expression of target genes at the transcription level .…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid‐transactivated TSC22D3 attenuates hypoxia‐ and diabetes‐induced Müller glial galectin‐1 expression via HIF‐1α destabilization

Kanda

Hirose

Noda

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Galectin-1/LGALS1, a newly recognized angiogenic factor, contributes to the pathogenesis of diabetic retinopathy (DR). Recently, we demonstrated that glucocorticoids suppressed an interleukin-1β-driven inflammatory pathway for galectin-1 expression in vitro and in vivo. Here, we show glucocorticoid-mediated inhibitory mechanism against hypoxia-inducible factor (HIF)-1α-involved galectin-1 expression in human Müller glial cells and the retina of diabetic mice. Hypoxia-induced increases in galectin-1/LGALS1 expression and promoter activity were attenuated by dexamethasone and triamcinolone acetonide in vitro. Glucocorticoid application to hypoxia-stimulated cells decreased HIF-1α protein, but not mRNA, together with its DNA-binding activity, while transactivating TSC22 domain family member (TSC22D)3 mRNA and protein expression. Co-immunoprecipitation revealed that glucocorticoid-transactivated TSC22D3 interacted with HIF-1α, leading to degradation of hypoxia-stabilized HIF-1α via the ubiquitin-proteasome pathway. Silencing TSC22D3 reversed glucocorticoid-mediated ubiquitination of HIF-1α and subsequent down-regulation of HIF-1α and galectin-1/LGALS1 levels. Glucocorticoid treatment to mice significantly alleviated diabetes-induced retinal HIF-1α and galectin-1/Lgals1 levels, while increasing TSC22D3 expression. Fibrovascular tissues from patients with proliferative DR demonstrated co-localization of galectin-1 and HIF-1α in glial cells partially positive for TSC22D3. These results indicate that glucocorticoid-transactivated TSC22D3 attenuates hypoxia-and diabetes-induced retinal glial galectin-1/LGALS1 expression via HIF-1α destabilization, highlighting therapeutic implications for DR in the era of anti-vascular endothelial growth factor treatment. K E Y W O R D S diabetic retinopathy, galectin-1, glucocorticoid, HIF-1α, hypoxia, Müller glia, transactivation, TSC22D3

show abstract

“…Similarly, GILZ overexpression protects against endoplasmic reticulum stress-mediated cell death, likely via the stimulation of mitochondrial oxidative phosphorylation (André et al, 2016). Further, the overexpression of GILZ is protective of the retina against light-induced cellular damage via the activation of antiapoptotic pathways (Gu et al, 2017). Despite the reported prosurvival and cytoprotective effects of GILZ, a recent report (Espinasse et al, 2016) indicates that GILZ overexpression in PLB-985 cells (which can differentiate into mature neutrophils) exacerbates apoptosis in association with the activation of caspase-9 and caspase-3 as well as the loss of mitochondrial potential.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid-Induced Leucine Zipper Promotes Neutrophil and T-Cell Polarization with Protective Effects in Acute Kidney Injury

Baban

Marchetti

Khodadadi

et al. 2018

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The glucocorticoid-induced leucine zipper (GILZ) mediates antiinflammatory effects of glucocorticoids. Acute kidney injury (AKI) mobilizes immune/inflammatory mechanisms, causing tissue injury, but the impact of GILZ in AKI is not known. Neutrophils play context-specific proinflammatory [type 1 neutrophil (N1)] and anti-inflammatory [type 2 neutrophil (N2)] functional roles. Also, regulatory T lymphocytes (Tregs) and regulatory T-17 (Treg17) cells exert counterinflammatory effects, including the suppression of effector T lymphocytes [e.g., T-helper (Th) 17 cells]. Thus, utilizing cell preparations of mice kidneys subjected to AKI or sham operation, we determined the effects of GILZ on T cells and neutrophil subtypes in the context of its renoprotective effect; these studies used the transactivator of transcription (TAT)-GILZ or the TAT peptide. AKI increased N1 and Th-17 cells but reduced N2, Tregs, and Treg17 cells in association with increased interleukin (IL)-17 1 but reduced IL-10 1 cells accompanied with the disruption of mitochondrial membrane potential (c m ) and increased apoptosis/necrosis compared with sham kidneys. TAT-GILZ, compared with TAT, treatment reduced N1 and Th-17 cells but increased N2 and Tregs, without affecting Treg17 cells, in association with a reduction in IL-17 1 cells but an increase in IL-10 1 cells; TAT-GILZ caused less disruption of c m and reduced cell death in AKI. Importantly, TAT-GILZ increased perfusion of the ischemicreperfused kidney but reduced tissue edema compared with TAT. Utilizing splenic T cells and bone marrow-derived neutrophils, we further showed marked reduction in the proliferation of Th cells in response to TAT-GILZ compared with response to TAT. Collectively, the results indicate that GILZ exerts renoprotection accompanied by the upregulation of the regulatory/suppressive arm of immunity in AKI, likely via regulating cross talk between T cells and neutrophils.

show abstract

Glucocorticoid-Induced Leucine Zipper Protects the Retina From Light-Induced Retinal Degeneration by Inducing Bcl-xL in Rats

Abstract: Overexpression of GILZ by OE-GILZ-rLV transduction protected the retina from light-induced cellular damage by activating antiapoptotic pathways.

Cited by 19 publications

References 45 publications

Photobiomodulation Mediates Neuroprotection against Blue Light Induced Retinal Photoreceptor Degeneration

Photobiomodulation Mediates Neuroprotection against Blue Light Induced Retinal Photoreceptor Degeneration

Glucocorticoid‐transactivated TSC22D3 attenuates hypoxia‐ and diabetes‐induced Müller glial galectin‐1 expression via HIF‐1α destabilization

Glucocorticoid-Induced Leucine Zipper Promotes Neutrophil and T-Cell Polarization with Protective Effects in Acute Kidney Injury

Contact Info

Product

Resources

About