Sequestosome1/p62: A regulator of redox-sensitive voltage-activated potassium channels, arterial remodeling, inflammation, and neurite outgrowth

Ishii, Tetsuro; Warabi, Eiji; Siow, Richard; Mann, Giovanni E.

doi:10.1016/j.freeradbiomed.2013.06.019

Cited by 49 publications

(34 citation statements)

References 154 publications

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“…These targets include cytoprotective phase-II enzymes and antioxidant enzymes such as heme oxygenase-1 (HO-1), superoxide dismutase-1 (SOD1) and others (Jaramillo and Zhang 2013; Leinonen et al, 2014). In vascular and hepatic cells at least, p62/sequestosome-1 (SQSTM1) is amongst the suite of Nrf2 regulated proteins whose expression increases upon Nrf2 activation (Ishii et al, 2013; 2004). Therefore, oxidative stress can stimulate subsets of autophagy gene expression, and particularly p62/SQSTM1 expression, via Nrf2 activation.…”

Section: Redox Regulation Is a Normal Feature Of Autophagy Whose Disrmentioning

confidence: 99%

Redox regulation of autophagy in healthy brain and neurodegeneration

Hensley

Harris-White

2015

Neurobiology of Disease

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Autophagy and redox biochemistry are two major sub disciplines of cell biology which are both coming to be appreciated for their paramount importance in the etiology of neurodegenerative diseases including Alzheimer’s disease (AD). Thus far, however, there has been relatively little exploration of the interface between autophagy and redox biology. Autophagy normally recycles macro-molecular aggregates produced through oxidative-stress mediated pathways, and also may reduce the mitochondrial production of reactive oxygen species through recycling of old and damaged mitochondria. Conversely, dysfunction in autophagy initiation, progression or clearance is evidenced to increase aggregation-prone proteins in neural and extraneural tissues. Redox mechanisms of autophagy regulation have been documented at the level of cross-talk between the Nrf2/Keap1 oxidant and electrophilic defense pathway and p62/sequestosome-1 (SQSTM1)-associated autophagy, at least in extraneural tissue; but other mechanisms of redox autophagy regulation doubtless remain to be discovered and the relevance of such processes to maintenance of neural homeostasis remain to be determined. This review summarizes current knowledge regarding the relationship of redox signaling, autophagy control, and oxidative stress as these phenomena relate to neurodegenerative disease. AD is specifically addressed as an example of the theme and as a promising indication for new therapies that act through engagement of autophagy pathways. To exemplify one such novel therapeutic entity, data is presented that the antioxidant and neurotrophic agent lanthionine ketimine-ethyl ester (LKE) affects autophagy pathway proteins including beclin-1 in the 3xTg-AD model of Alzheimer’s disease where the compound has been shown to reduce pathological features and cognitive dysfunction.

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Section: Redox Regulation Is a Normal Feature Of Autophagy Whose Disrmentioning

confidence: 99%

Redox regulation of autophagy in healthy brain and neurodegeneration

Hensley

Harris-White

2015

Neurobiology of Disease

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“…HO-1 and Prx1 are well known endogenous antioxidants, and enhanced expression of these proteins and increases GSH via xCT up regulation ensure protection of cells against oxidative damage. Sequestosome1/p62 is a modulator of cell signaling with multifunctional activities including anti-inflammatory functions [44,45]. …”

Section: Nrf2-mediated Regulation Of Redox Balance In Cultured Cellsmentioning

confidence: 99%

Redox status in mammalian cells and stem cells during culture in vitro: Critical roles of Nrf2 and cystine transporter activity in the maintenance of redox balance

2014

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Culturing cells and tissues in vitro has provided valuable insights into the molecular mechanisms regulating redox signaling in cells with implications for medicine. However, standard culture techniques maintain mammalian cells in vitro under an artificial physicochemical environment such as ambient air and 5% CO2. Oxidative stress is caused by the rapid oxidation of cysteine to cystine in culture media catalyzed by transition metals, leading to diminished intracellular cysteine and glutathione (GSH) pools. Some cells, such as fibroblasts and macrophages, express cystine transport activity, designated as system xc-, which enables cells to maintain these pools to counteract oxidative stress. Additionally, many cells have the ability to activate the redox sensitive transcription factor Nrf2, a master regulator of cellular defenses against oxidative stress, and to upregulate xCT, the subunit of the xc- transport system leading to increases in cellular GSH. In contrast, some cells, including lymphoid cells, embryonic stem cells and iPS cells, express relatively low levels of xCT and cannot maintain cellular cysteine and GSH pools. Thus, fibroblasts have been used as feeder cells for the latter cell types based on their ability to supply cysteine. Other key Nrf2 regulated gene products include heme oxygenase 1, peroxiredoxin 1 and sequestosome1. In macrophages, oxidized LDL activates Nrf2 and upregulates the scavenger receptor CD36 forming a positive feedback loop to facilitate removal of the oxidant from the vascular microenvironment. This review describes cell type specific responses to oxygen derived stress, and the key roles that activation of Nrf2 and membrane transport of cystine and cysteine play in the maintenance and proliferation of mammalian cells in culture.

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“…In the present review, we focus on the emerging roles of p62 in mTORC1 activation, the Keap1-Nrf2 pathway, and selective autophagy. Functions of p62/Sqstm1 not covered in this review are discussed elsewhere [1][2][3][4][5]11].…”

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confidence: 99%

p62/SQSTM1 functions as a signaling hub and an autophagy adaptor

2015

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and ichimura-ys@med.niigata-u.ac.jp p62/SQSTM1 is a stress-inducible cellular protein that is conserved among metazoans 20 but not in plants and fungi. p62/SQSTM1 has multiple domains that mediate its interactions with various binding partners, and it serves as a signaling hub for diverse cellular events such as amino-acid sensing and the oxidative stress response. In addition, p62/SQSTM1 functions as a selective autophagy receptor for degradation of ubiqutinated substrates. Herein we delineate the current knowledge about p62 with regard to mTORC1 25 activation, the Keap1-Nrf2 pathway, and selective autophagy.

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Sequestosome1/p62: A regulator of redox-sensitive voltage-activated potassium channels, arterial remodeling, inflammation, and neurite outgrowth

Cited by 49 publications

References 154 publications

Redox regulation of autophagy in healthy brain and neurodegeneration

Redox regulation of autophagy in healthy brain and neurodegeneration

Redox status in mammalian cells and stem cells during culture in vitro: Critical roles of Nrf2 and cystine transporter activity in the maintenance of redox balance

p62/SQSTM1 functions as a signaling hub and an autophagy adaptor

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