Nrf2-dependent Induction of Proteasome and Pa28αβ Regulator Are Required for Adaptation to Oxidative Stress

Pickering, Andrew M.; Linder, Robert A.; Zhang, Hongqiao; Forman, Henry Jay; Davies, Kelvin J.A.

doi:10.1074/jbc.m111.277145

Cited by 255 publications

(238 citation statements)

References 67 publications

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“…Related to oxidative stress, it has been observed a NRF2-dependent induction of proteasome required for adaptation to the stress [55]. These data were corroborated by the fact that an NRF2 inducer, sulforaphane (SFN), increases the expression of NRF2-regulated genes as well as the expression of the catalytic subunits of the proteasome and proteasomal peptidase activities [56,57].…”

Section: Nrf2 Modulation Of Proteostasis Oxidative Stress and Inflamsupporting

confidence: 65%

Role of the Transcription Factor Nrf2 in Parkinson’s Disease: New Insights

Lastres‐Becker¹

2017

J Alzheimers Dis Parkinsonism

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Section: Nrf2 Modulation Of Proteostasis Oxidative Stress and Inflamsupporting

confidence: 65%

Role of the Transcription Factor Nrf2 in Parkinson’s Disease: New Insights

Lastres‐Becker¹

2017

J Alzheimers Dis Parkinsonism

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“…A complimentary possibility is that proteasomal insufficiency in affected rods is caused by misbalance in the protein ubiquitination/deubiquitination system. These data further indicate that photoreceptors experiencing proteasomal insufficiency in the course of their progressive degeneration are essentially defenseless against this condition, due to a lack of compensatory mechanisms that allow proteasomal activity enhancement, such as those used in response to acute oxidative stress (26).…”

Section: Gβmentioning

confidence: 90%

Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration

Lobanova

Finkelstein

Skiba

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Inherited retinal degenerations, caused by mutations in over 100 individual genes, affect approximately 2 million people worldwide. Many of the underlying mutations cause protein misfolding or mistargeting in affected photoreceptors. This places an increased burden on the protein folding and degradation machinery, which may trigger cell death. We analyzed how these cellular functions are affected in degenerating rods of the transducin γ-subunit (Gγ 1 ) knockout mouse. These rods produce large amounts of transducin β-subunit (Gβ 1 ), which cannot fold without Gγ 1 and undergoes intracellular proteolysis instead of forming a transducin βγ-subunit complex. Our data revealed that the most critical pathobiological factor leading to photoreceptor cell death in these animals is insufficient capacity of proteasomes to process abnormally large amounts of misfolded protein. A decrease in the Gβ 1 production in Gγ 1 knockout rods resulted in a significant reduction in proteasomal overload and caused a striking reversal of photoreceptor degeneration. We further demonstrated that a similar proteasomal overload takes place in photoreceptors of other mutant mice where retinal degeneration has been ascribed to protein mistargeting or misfolding, but not in mice whose photoreceptor degenerate as a result of abnormal phototransduction. These results establish the prominence of proteasomal insufficiency across multiple degenerative diseases of the retina, thereby positioning proteasomes as a promising therapeutic target for treating these debilitating conditions. neurodegenerative diseases | protein degradation

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“…43 As an adaptation to hydrogen peroxide and menadione-induced oxidative stress, up-regulation of Nrf2 induces the expression of 26S proteosome and Pa28ab regulator. 44 Nrf2-induced proteosomal activity and expression of 20S and 19S proteosome subunits have been demonstrated in murine liver. 45 Induction of the DNA glycosylase, 8-oxoguanine glycosylase, expression via Nrf2 signaling has been shown to inhibit reactive oxygen species (ROS)-mediated DNA damage in breast cancer.…”

Section: Nrf2 In Cellular Redox Homeostasismentioning

confidence: 95%

Nuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis

Swamy

Rajasekaran

Thannickal

2016

The American Journal of Pathology

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Aging and age-related diseases have been associated with elevated oxidative stress, which may be related to increased production of reactive species and/or a deficiency in antioxidant defenses. The nuclear factor-erythroid-2erelated factor 2 (Nrf2)-mediated antioxidant response pathway maintains cellular reduction-oxidation homeostasis by inducing the transcription of an array of cytoprotective genes. However, there is evidence of impaired Nrf2 response in aging contributing to age-related fibrotic diseases. Herein, we review mechanisms for the dysregulation of Nrf2 signaling in aging. This understanding will pave the way for the design of novel therapeutic strategies that restore Nrf2 signaling to reestablish cellular homeostasis in aging and age-related fibrotic diseases.

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Nrf2-dependent Induction of Proteasome and Pa28αβ Regulator Are Required for Adaptation to Oxidative Stress

Cited by 255 publications

References 67 publications

Role of the Transcription Factor Nrf2 in Parkinson’s Disease: New Insights

Role of the Transcription Factor Nrf2 in Parkinson’s Disease: New Insights

Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration

Nuclear Factor–Erythroid-2–Related Factor 2 in Aging and Lung Fibrosis

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