Redox Control of the Senescence Regulator Interleukin-1α and the Secretory Phenotype

McCarthy, Donald A; Clark, Ryan R.; Bartling, Toni R.; Trebak, Mohamed; Melendez, J. Andrés

doi:10.1074/jbc.m113.493841

Cited by 71 publications

(77 citation statements)

References 40 publications

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“…Our observations suggest that senescent disc cells also prefer to 82 aggregate in monolayer cultures (Fig.3). As one of the pathological features for 83 degeneration, cell clusters are commonly found in the NP and the inner AF where 84 significant histopathological changes are evident 30, 31 . In some discs at an advanced M A N U S C R I P T A C C E P T E D to experience further nutritional deficiency and oxygen deprivation 58 .…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration

Wang

Cai

Shi

et al. 2016

Osteoarthritis and Cartilage

368

301

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Intervertebral disc (IVD) degeneration is a complicated process that involves both age-related change and tissue damage caused by multiple stresses. In a degenerative IVD, cellular senescence accumulates and is associated with reduced proliferation, compromised self-repair, increased inflammatory response, and enhanced catabolic metabolism. In this review, we decipher the senescence mechanism of IVD degeneration (IVDD) by interpreting how aging coordinates with age-related, microenvironment-derived stresses in promoting disc cell senescence and accelerating IVDD. After chronic and prolonged replication, cell senescence may occur as a natural part of the disc aging process, but can potentially be accelerated by growth factor deficiency, oxidative accumulation, and inflammatory irritation. While acute disc injury, excessive mechanical overloading, diabetes, and chronic tobacco smoking contribute to the amplification of senescence-inducing stresses, the avascular nature of IVD impairs the immune-clearance of the senescent disc cells, which accumulate in cell clusters, demonstrate inflammatory and catabolic phenotypes, deteriorate disc microenvironment, and accelerate IVDD. Anti-senescence strategies, including telomerase transduction, supply of growth factors, and blocking cell cycle inhibitors, have been shown to be feasible in rescuing disc cells from early senescence, but their efficiency for disc regeneration requires more in vivo validations. Guidelines dedicated to avoiding or alleviating senescence-inducing stresses might decelerate cellular senescence and benefit patients with IVD degenerative diseases.

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Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration

Wang

Cai

Shi

et al. 2016

Osteoarthritis and Cartilage

368

301

View full text Add to dashboard Cite

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“…The following examples further illustrate the use of kinetically controlled systems in nuclear protein trafficking and in maintenance of the integrity of the genome. Recent reviews are also available on the redox processing in the secretory pathway [33, 34, 120] and in mitochondrial import [35, 36]. Relatively less information is available on vectorial redox processing during endocytosis and proteolysis in lysosomes, but evidence is available suggesting that analogous systems are present [121, 122].…”

Section: Protein Cys Redox Regulationmentioning

confidence: 99%

The cysteine proteome

Chandler

Jones

2015

Free Radical Biology and Medicine

314

243

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The cysteine (Cys) proteome is a major component of the adaptive interface between the genome and the exposome. The thiol moiety of Cys undergoes a range of biologic modifications enabling biological switching of structure and reactivity. These biological modifications include sulfenylation and disulfide formation, formation of higher oxidation states, S-nitrosylation, persulfidation, metallation, and other modifications. Extensive knowledge about these systems and their compartmentalization now provides a foundation to develop advanced integrative models of Cys proteome regulation. In particular, detailed understanding of redox signaling pathways and sensing networks is becoming available to discriminate network structures. This research focuses attention on the need for atlases of Cys modifications to develop systems biology models. Such atlases will be especially useful for integrative studies linking the Cys proteome to imaging and other omics platforms, providing a basis for improved redox-based therapeutics. Thus, a framework is emerging to place the Cys proteome as a complement to the quantitative proteome in the omics continuum connecting the genome to the exposome.

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“…Apoptotic endothelial cells contain the full-length IL-1a precursor (70); IL-1alpha appears to be a DNA damage sensor (71) and play a role in cellular senescence (72). Whether IL-1 alpha plays an important role in inflammation and autoimmunity in PAH remains to be investigated.…”

Section: Cytokines Chemoattraction Activated Lung Microvascular mentioning

confidence: 99%

Challenges and opportunities in treating inflammation associated with pulmonary hypertension

Voelkel

Tamošiūnienė

Nicolls

2016

Expert Review of Cardiovascular Therapy

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Inflammatory cells are present in the lungs from patients with many, if not all, forms of severe pulmonary hypertension. Historically the first inflammatory cell identified in the pulmonary vascular lesions was the mast cell. T and B lymphocytes, as well as macrophages, are present in and around the pulmonary arterioles and many patients have elevated blood levels of interleukin 1 and 6; some patients show elevated levels of leukotriene B4. An overlap between collagen-vascular disease-associated pulmonary arterial hypertension (PAH) and idiopathic PAH exists, yet only a few studies have been designed that evaluate the effect of anti-inflammatory treatments. Here we review the pertinent data that connect PAH and inflammation/immune dysregulation and evaluate experimental models of severe PAH with an emphasis on the Sugen/athymic rat model of severe PAH. We postulate that there are more than one inflammatory phenotype and predict that there will be several anti-inflammatory treatment strategies for severe PAH.

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Redox Control of the Senescence Regulator Interleukin-1α and the Secretory Phenotype

Cited by 71 publications

References 40 publications

Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration

Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration

The cysteine proteome

Challenges and opportunities in treating inflammation associated with pulmonary hypertension

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