Lipofuscin: formation, effects and role of macroautophagy

Höhn, Annika; Grune, Tilman

doi:10.1016/j.redox.2013.01.006

Cited by 241 publications

(167 citation statements)

References 52 publications

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“…Direct intake of degradable material into lysosomes is called microautophagy (115). In contrast, macroautophagy describes the inclusion of organelles and soluble proteins, first into double-membrane structures (phagophores), generating double-membrane vesicles, called autophagosomes, which afterward merge with the lysosomes (65,76). Compared with microautophagy and macroautophagy, substrate uptake via CMA is a more substrate-specific process.…”

Section: Repair and Degradation Of Oxidized Proteinsmentioning

confidence: 99%

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

Reeg

Grune

2015

Antioxidants & Redox Signaling

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157

123

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Significance: A constant accumulation of oxidized proteins takes place during aging. Oxidation of proteins leads to a partial unfolding and, therefore, to aggregation. Protein aggregates impair the activity of cellular proteolytic systems (proteasomes, lysosomes), resulting in further accumulation of oxidized proteins. In addition, the accumulation of highly crosslinked protein aggregates leads to further oxidant formation, damage to macromolecules, and, finally, to apoptotic cell death. Furthermore, protein oxidation seems to play a role in the development of various age-related diseases, for example, neurodegenerative diseases. Recent Advances: The highly oxidized lipofuscin accumulates during aging. Lipofuscin formation might cause impaired lysosomal and proteasomal degradation, metal ion accumulation, increased reactive oxygen species formation, and apoptosis. Critical Issues: It is still unclear to which extent protein oxidation is involved in the progression of aging and in the development of some age-related diseases. Future Directions: An extensive knowledge of the effects of protein oxidation on the aging process and its contribution to the development of age-related diseases could enable further strategies to reduce age-related impairments. Strategies aimed at lowering aggregate formation might be a straightforward intervention to reduce age-related malfunctions of organs. Antioxid. Redox Signal. 23, 239-255.

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Section: Repair and Degradation Of Oxidized Proteinsmentioning

confidence: 99%

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

Reeg

Grune

2015

Antioxidants & Redox Signaling

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157

123

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“…Aging predisposes to structural and functional impairment of liver as well as various changes in liver cells which is associated with increased risk of hepatic injury (Schmucker 2005;Hohn & Grune 2013). Aging is also associated with increased lipid accumulation in nonadipose tissues, including the liver.…”

Section: Introductionmentioning

confidence: 99%

Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice

Kim

Liu

et al. 2016

AGE

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We aimed to investigate whether aging increases the susceptibility of hepatic and renal inflammation or fibrosis in response to high-fat diet (HFD) and explore the underlying genetic alterations. Middle (10 months old) and old (20 months old) aged, male C57BL/6N mice were fed either a low-fat diet (4 % fat) or HFD (60 % fat) for 4 months. Young (3 months old) aged mice were included as control group. HFDinduced liver and kidney injuries were analyzed by serum and urine assay, histologic staining, immunohistochemistry, and reverse-transcription real-time quantitative polymerase chain reaction. Total RNA sequencing with next-generation technology was done with RNA extracted from liver tissues. With HFD feeding, aged was associated with higher serum alanine aminotransferase levels, marked infiltration of hepatic macrophages, and increased expression of inflammatory cytokines (MCP1, TNF-α, IL-1β, IL-6, IL-12, IL-17A). Importantly, aged mice showed more advanced hepatic fibrosis and increased expression of fibrogenic markers (Col-I-α1, αSMA, TGF-β1, TGF-β2, TGFβRII, PDGF, PDGFRβII, TIMP1) in response to HFD. Aged mice fed on HFD also showed increased oxidative stress and TLR4 expression. In the total RNA seq and gene ontology analysis of liver, old-aged HFD group showed significant up-regulation of genes linked to innate immune response, immune response, defense response, inflammatory response compared to middle-aged HFD group. Meanwhile, aging and HFD feeding showed significant increase in glomerular size and mesangial area, higher urine albumin/creatinine ratio, and advanced renal inflammation or fibrosis. However, the difference of HFD-induced renal injury between oldaged group and middle-aged group was not significant. The susceptibility of hepatic fibrosis as well as hepatic inflammation in response to HFD was significantly increased with aging. In addition, aging was associated with glomerular alterations and increased renal inflammation or fibrosis, while the differential effect of aging AGE (2016) 38:291-302

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“…While aggresomes are observed to have a protective role in the cell, aggresomes can interfere with proteosomal activity (Höhn & Grune, 2013) and long‐term exposure have led to DNA damage and cell cycle arrest (Lu, Boschetti, & Tunnacliffe, 2015). Evaluation of the longer‐term effect on cell growth revealed Cu OAC treatment to have a negative long‐term impact on cellular growth of Caco‐2 and may be related to aggresomes detected Cu OAC‐treated cells.…”

Section: Discussionmentioning

confidence: 99%

Acute exposure to organic and inorganic sources of copper: Differential response in intestinal cell lines

Keenan

O’Sullivan

Henry

et al. 2018

Food Science & Nutrition

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ScopeCopper supplementation in nutrition has evolved from using inorganic mineral salts to organically chelated minerals but with limited knowledge of the impact at the cellular level.MethodsHere, the impact of inorganic and organic nutrient forms (glycinate, organic acid, and proteinate) of copper on the cellular level is investigated on intestinal cell lines, HT29 and Caco‐2, after a 2‐hr acute exposure to copper compounds and following a 10‐hr recovery.ResultsFollowing the 10‐hr recovery, increases were observed in proteins involved in metal binding (metallothioneins) and antioxidant response (sulfiredoxin 1 and heme oxygenase 1), and global proteomic analysis suggested recruitment of the unfolded protein response and proteosomal overloading. Copper organic acid chelate, the only treatment to show striking and sustained reactive oxygen species generation, had the greatest impact on ubiquitinated proteins, reduced autophagy, and increased aggresome formation, reducing growth in both cell lines. The least effect was noted in copper proteinate with negligible impact on aggresome formation or extended growth for either cell line.ConclusionThe type and source of copper can impact significantly at the cellular level.

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Lipofuscin: formation, effects and role of macroautophagy

Cited by 241 publications

References 52 publications

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice

Acute exposure to organic and inorganic sources of copper: Differential response in intestinal cell lines

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