Proteasomal degradation of glycated proteins depends on substrate unfolding: Preferred degradation of moderately modified myoglobin

Raupbach, Jana; Ott, Christiane; Koenig, Jeannette; Grune, Tilman

doi:10.1016/j.freeradbiomed.2019.11.024

Cited by 19 publications

(16 citation statements)

References 38 publications

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“…Pharmacological proteasomal inhibition boosts the accumulation of AGEs in vitro in RPE-derived cells [132]. However, excessive glycative stress decreases proteasomal capacity via the formation of intermolecular crosslinks that, consequently, lead to accelerated accumulation of AGEs [136][137][138].…”

Section: Proteolytic Pathways: the Last Line Of Defense Against Glycation-derived Damagementioning

confidence: 99%

Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

et al. 2020

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Hyperglycemia, a defining characteristic of diabetes, combined with oxidative stress, results in the formation of advanced glycation end products (AGEs). AGEs are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote the formation of reactive oxygen species (ROS), which, in turn, boost the production of AGEs, resulting in positive feedback loops, a vicious cycle that compromises tissue fitness. Oxidative stress and the accumulation of AGEs are etiologically associated with the pathogenesis of multiple diseases including diabetic retinopathy (DR). DR is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach to slow this sight-threatening diabetic complication. To set DR in a physiological context, in this review we first describe relations between oxidative stress, formation of AGEs, and aging in several tissues of the eye, each of which is associated with a major age-related eye pathology. We summarize mechanisms of AGEs generation and anti-AGEs detoxifying systems. We specifically feature the potential of the glyoxalase system in the retina in the prevention of AGEs-associated damage linked to DR. We provide a comparative analysis of glyoxalase activity in different tissues from wild-type mice, supporting a major role for the glyoxalase system in the detoxification of AGEs in the retina, and present the manipulation of this system as a therapeutic strategy to prevent the onset of DR.

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Section: Proteolytic Pathways: the Last Line Of Defense Against Glycation-derived Damagementioning

confidence: 99%

Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

et al. 2020

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“…Methylglyoxal is also a substrate of CEL [ 38 ]. It was noted that incubation of myoglobin with methylglyoxal resulted in the increased formation of pentosidine [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Advanced Glycation End-Products (AGEs) and Their Soluble Receptor (sRAGE) in Women Suffering from Systemic Lupus Erythematosus (SLE)

Nowak

Przywara-Chowaniec

Damasiewicz-Bodzek

et al. 2021

Cells

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Systemic lupus erythematosus (SLE) is characterized by abnormal action of the immune system and a state of chronic inflammation. The disease can cause life-threatening complications. Neoepitopes arising from interdependent glycation and oxidation processes might be an element of SLE pathology. The groups included in the study were 31 female SLE patients and 26 healthy female volunteers (the control group). Blood serum samples were obtained to evaluate concentrations of advanced glycation end-products (AGEs), carboxymethyllysine (CML), carboxyethyllysine (CEL), pentosidine, and a soluble form of the receptor for advanced glycation end-products (sRAGE). Compared to a healthy control group, the SLE patients exhibited a higher concentration of AGEs and a lower concentration of sRAGE in serum. There were no statistically significant differences in serum CML, CEL, and pentosidine concentrations between the groups. Therefore, SLE patients could be at risk of intensified glycation process and activation of the proinflammatory receptor for advanced glycation end-products (RAGE), which could potentially worsen the disease course; however, it is not clear which compounds contribute to the increased concentration of AGEs in the blood. Additionally, information about the cigarette smoking and alcohol consumption of the study participants was obtained.

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“…The d -ribose or d -glucose with the final concentration of 0.5 mmol/L was added into the HMb solution (0.1 mmol/L, final concentration) [ 15 , 20 , 23 ]. After the filtration and sterilization, the mixed solution was incubated at 37 °C for 1–24 h. Under the same conditions, the HMb solution without the added d -ribose or d -glucose was used as the control.…”

Section: Methodsmentioning

confidence: 99%

“…Comparatively, the protein glycation of other globins in the organism, such as myoglobin ((Mb), Figure 1 , left), is less studied [ 20 , 21 , 22 , 23 , 24 ]. In addition to the biological function of O 2 storage and transportation, Mb may also exhibit multiple biological functions, such as serving as a nitric oxide (NO) scavenger and a hypoxic nitrite reductase (NIR) [ 25 , 26 , 27 ], as well as a peroxidase using H 2 O 2 as an oxidant [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…When these cells are damaged, Mb can quickly enter the blood circulation and undergo protein glycation with carbohydrates such as glucose, resulting in modifications to the protein structure and function [20]. Recently, Grune et al showed that the proteasome prefers to degrade the glucose-modified Mb [23]. As a naturally occurring pentose sugar, D-ribose is widely used in food, medicine, cosmetics, etc.…”

Section: Introductionmentioning

confidence: 99%

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Identification of the Protein Glycation Sites in Human Myoglobin as Rapidly Induced by d-Ribose

et al. 2021

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Protein glycation is an important protein post-translational modification and is one of the main pathogenesis of diabetic angiopathy. Other than glycated hemoglobin, the protein glycation of other globins such as myoglobin (Mb) is less studied. The protein glycation of human Mb with ribose has not been reported, and the glycation sites in the Mb remain unknown. This article reports that d-ribose undergoes rapid protein glycation of human myoglobin (HMb) at lysine residues (K34, K87, K56, and K147) on the protein surface, as identified by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). Moreover, glycation by d-ribose at these sites slightly decreased the rate of the met heme (FeIII) in reaction with H2O2 to form a ferryl heme (FeIV=O). This study provides valuable insight into the protein glycation by d-ribose and provides a foundation for studying the structure and function of glycated heme proteins.

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Proteasomal degradation of glycated proteins depends on substrate unfolding: Preferred degradation of moderately modified myoglobin

Cited by 19 publications

References 38 publications

Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy

Advanced Glycation End-Products (AGEs) and Their Soluble Receptor (sRAGE) in Women Suffering from Systemic Lupus Erythematosus (SLE)

Identification of the Protein Glycation Sites in Human Myoglobin as Rapidly Induced by d-Ribose

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