Repertoires of Autophagy in the Pathogenesis of Ocular Diseases

Cellular Physiology and Biochemistry, Journal Year: 2015, Volume and Issue: 35(5), P. 1663 - 1676

Published: Jan. 1, 2015

Age-related macular degeneration (AMD) is the most common reason of visual impairment in elderly Western countries. The retinal pigment epithelial cells (RPE) causes secondarily adverse effects on neural retina leading to loss. aging characteristics RPE involve lysosomal accumulation lipofuscin and extracellular protein aggregates called "drusen". Molecular mechanisms behind aggregations are weakly understood. There intriguing evidence suggesting that SQSTM1/p62, together with autophagy, has a role pathology different degenerative diseases. It appears SQSTM1/p62 connecting link between autophagy proteasome mediated proteolysis, expressed strongly under exposure various oxidative stimuli proteasomal inhibition. ELAVL1/HuR post-transcriptional factor, which acts mainly as positive regulator gene expression by binding specific mRNAs whose corresponding proteins fundamental for key cellular functions. We here show that, inhibitor MG-132, up-regulated at both mRNA levels, this binds post-transcriptionally regulates ARPE-19 cell line. Furthermore, we observed inhibition caused bound irreversibly perinuclear aggregates. addition AMPK activator AICAR was pro-survival promoted cleansing former complex, but not accumulation, indeed decreased through autophagy-mediated degradation, while pathway. Interestingly, when compared human controls, AMD donor samples strong rather than drusen rich area impaired AMD.

Language: Английский

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Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism

Cellular and Molecular Life Sciences, Journal Year: 2016, Volume and Issue: 73(17), P. 3221 - 3247

Published: April 21, 2016

The multifunctional regulator nuclear factor erythroid 2-related (Nrf2) is considered not only as a cytoprotective regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it also powerful modulator species longevity. vertebrate Nrf2 belongs to Cap 'n' Collar (Cnc) bZIP family transcription factors shares high homology with SKN-1 from Caenorhabditis elegans or CncC found in Drosophila melanogaster. major characteristics are some extent mimicked by Nrf2-dependent their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions carbon monoxide. HO-1 products exert beneficial effects through protection against oxidative injury, regulation apoptosis, modulation inflammation well contribution angiogenesis. On other hand, disturbances proper level associated pathogenesis age-dependent disorders, neurodegeneration, cancer macular degeneration. This review summarizes our knowledge about across different phyla suggesting conservative role stress-protective anti-aging factors.

Language: Английский

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The Nrf2 regulatory network provides an interface between redox and intermediary metabolism

Trends in Biochemical Sciences, Journal Year: 2014, Volume and Issue: 39(4), P. 199 - 218

Published: March 20, 2014

Language: Английский

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Antioxidant responses and cellular adjustments to oxidative stress

Redox Biology, Journal Year: 2015, Volume and Issue: 6, P. 183 - 197

Published: July 21, 2015

Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in scenarios. This review focuses on role crucial cellular nucleophiles, such as glutathione, their capacity interact with oxidants establish networks other critical enzymes peroxiredoxins. We discuss importance Nrf2-Keap1 pathway an example a transcriptional response we summarize routes related redox activation. As examples tissular settings where major players highlight endoplasmic reticulum stress ischemia reperfusion. Topologically confined redox-mediated post-translational modifications thiols considered important molecular mechanisms mediating many responses, whereas redox-sensitive microRNAs have emerged key posttranscriptional regulation gene expression. Understanding may provide basis for antioxidant-based therapeutic interventions redox-related diseases.

Language: Английский

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The emerging role of Nrf2 in mitochondrial function

Free Radical Biology and Medicine, Journal Year: 2015, Volume and Issue: 88, P. 179 - 188

Published: May 11, 2015

The transcription factor NF-E2 p45-related 2 (Nrf2; gene name NFE2L2) allows adaptation and survival under conditions of stress by regulating the expression diverse networks cytoprotective proteins, including antioxidant, anti-inflammatory, detoxification enzymes as well proteins that assist in repair or removal damaged macromolecules. Nrf2 has a crucial role maintenance cellular redox homeostasis biosynthesis, utilization, regeneration glutathione, thioredoxin, NADPH controlling production reactive oxygen species mitochondria oxidase. Under homeostatic conditions, affects mitochondrial membrane potential, fatty acid oxidation, availability substrates (NADH FADH2/succinate) for respiration, ATP synthesis. growth stimulation, activation counteracts increased via transcriptional upregulation uncoupling protein 3 influences biogenesis maintaining levels nuclear respiratory 1 peroxisome proliferator-activated receptor γ coactivator 1α, promoting purine nucleotide biosynthesis. Pharmacological activators, such naturally occurring isothiocyanate sulforaphane, inhibit oxidant-mediated opening permeability transition pore swelling. Curiously, synthetic 1,4-diphenyl-1,2,3-triazole compound, originally designed an activator, was found to promote mitophagy, thereby contributing overall homeostasis. Thus, is prominent player supporting structural functional integrity mitochondria, this particularly stress.

Language: Английский

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Oxidative pathways of chemical toxicity and oxidative stress biomarkers in marine organisms

Marine Environmental Research, Journal Year: 2013, Volume and Issue: 93, P. 106 - 117

Published: July 25, 2013

Language: Английский

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Small Molecule Modulators of Keap1‐Nrf2‐ARE Pathway as Potential Preventive and Therapeutic Agents

Medicinal Research Reviews, Journal Year: 2012, Volume and Issue: 32(4), P. 687 - 726

Published: May 1, 2012

Abstract K elch‐like ECH ‐associated protein 1 ( eap1)‐nuclear factor erythroid 2‐related 2 N rf2)‐antioxidant response elements ARE ) pathway represents one of the most important cellular defense mechanisms against oxidative stress and xenobiotic damage. Activation rf2 signaling induces transcriptional regulation ARE‐dependent expression various detoxifying antioxidant enzymes proteins. Keap1‐Nrf2‐ARE has become an attractive target for prevention treatment stress‐related diseases conditions including cancer, neurodegenerative, cardiovascular, metabolic, inflammatory diseases. Over last few decades, numerous inducers have been developed some them are currently undergoing clinical trials. Recently, overactivation implicated in cancer progression as well drug resistance to chemotherapy. Thus, inhibitors could potentially be used improve effectiveness therapy. Herein, we review mechanism eap1‐ rf2‐ pathway, its disease relevance, known classes small molecule modulators. We also discuss several aspects eap1– interaction, rf2‐based peptide inhibitor design, screening assays discovery direct interaction. © 2012 Wiley Periodicals, Inc. Med Res Rev., 32, No. 4, 687‐726,

Language: Английский

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The Dual Roles of NRF2 in Cancer

Trends in Molecular Medicine, Journal Year: 2016, Volume and Issue: 22(7), P. 578 - 593

Published: June 3, 2016

Language: Английский

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Role of peroxisomes in ROS/RNS-metabolism: Implications for human disease

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2011, Volume and Issue: 1822(9), P. 1363 - 1373

Published: Dec. 11, 2011

Language: Английский

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Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection

Progress in Neurobiology, Journal Year: 2012, Volume and Issue: 100, P. 30 - 47

Published: Sept. 29, 2012

Language: Английский

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