Emerging role of post-translational modifications in chronic kidney disease and cardiovascular disease

Gajjala, Prathibha R.; Fliser, Danilo; Speer, Thimoteus; Jankowski, Vera; Jankowski, Joachim

doi:10.1093/ndt/gfv048

Cited by 88 publications

(89 citation statements)

References 96 publications

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“…At the proteomic level, differential levels of protein expression 253 and post-translational protein modifications resulting from altered gene expression or uraemic toxicity can be precisely defined, setting the stage for novel therapeutic approaches. For example, post-translational modifications that change protein half-life or function, such as carbamylation, or high levels of methylglyoxal-derived advanced glycation end-products have been identified in patients with uraemia 254 .…”

Section: A Systems Biology Approachmentioning

confidence: 99%

The systemic nature of CKD

et al. 2017

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The accurate definition and staging of chronic kidney disease (CKD) is one of the major achievements of modern nephrology. Intensive research is now being undertaken to unravel the risk factors and pathophysiologic underpinnings of this disease. In particular, the relationships between the kidney and other organs have been comprehensively investigated in experimental and clinical studies in the last two decades. Owing to technological and analytical limitations, these links have been studied with a reductionist approach focusing on two organs at a time, such as the heart and the kidney or the bone and the kidney. Here, we discuss studies that highlight the complex and systemic nature of CKD. Energy balance, innate immunity and neuroendocrine signalling are highly integrated biological phenomena. The diseased kidney disrupts such integration and generates a high-risk phenotype with a clinical profile encompassing inflammation, protein-energy wasting, altered function of the autonomic and central nervous systems and cardiopulmonary, vascular and bone diseases. A systems biology approach to CKD using omics techniques will hopefully enable in-depth study of the pathophysiology of this systemic disease, and has the potential to unravel critical pathways that can be targeted for CKD prevention and therapy.

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Section: A Systems Biology Approachmentioning

confidence: 99%

The systemic nature of CKD

et al. 2017

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“…Although isocyanate or thiocyanate produced under uremic conditions lead to carbamylation of amino acids and proteins but carbamylation of LDL is most relevant to the development of atherogenesis. Some other modifications of LDL have been identified that are linked to atherosclerotic plaque formation and progression [30]. Recent studies suggest that cLDL is a dominant form of modified LDL that occurs either by urea-derived cyanate or thiocyanate-derived cyanate generated by the enzyme MPO (myeloperoxidase) [4].…”

Section: Discussionmentioning

confidence: 99%

Carbamylated Low-Density Lipoprotein (cLDL)-Mediated Induction of Autophagy and Its Role in Endothelial Cell Injury

et al. 2016

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Patients with chronic kidney disease (CKD) have high risk of cardiovascular complications. Plasma levels of carbamylated proteins produced by urea-derived isocyanate or thiocyanate are elevated in CKD patients and that they are significant predictors of cardiovascular events and all-cause mortality. Carbamylated LDL (cLDL) has pro-atherogenic properties and is known to affect major biological processes relevant to atherosclerosis including endothelial cell injury. The underlying mechanisms of cLDL-induced endothelial cell injury are not well understood. Although autophagy has been implicated in atherosclerosis, cLDL-mediated induction of autophagy and its role in endothelial cell injury is unknown. Our studies demonstrate that human coronary artery endothelial cells (HCAECs) respond to cLDL by specific induction of key autophagy proteins including LC3-I, beclin-1, Atg5, formation of lipid-conjugated LC3-II protein, and formation of punctate dots of autophagosome-associated LC3-II. We demonstrated that autophagy induction is an immediate response to cLDL and occurred in a dose and time-dependent manner. Inhibition of cLDL-induced autophagy by a specific siRNA to LC3 as well as by an autophagy inhibitor provided protection from cLDL-induced cell death and DNA fragmentation. Our studies demonstrate that autophagy plays an important role in cLDL-mediated endothelial cell injury and may provide one of the underlying mechanisms for the pathogenesis of cLDL-induced atherosclerosis in CKD patients.

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“…9,24,25 It has also recently been shown that eosinophil peroxidase-mediated carbamylation of proteins can alter immune responses and give rise to a triggering of inflammatory signals in a similar way as could be seen in asthma. An increased carbamylation of proteins in vivo has been seen in patients with chronic kidney disease, characterized by elevated levels of urea and cyanate in the circulation and a possible increased risk of atherosclerosis.…”

Section: Concentration Of Ica Mic and Hcn In Frying Fumes (μG/m 3 ) Bmentioning

confidence: 96%

“…An increased carbamylation of proteins in vivo has been seen in patients with chronic kidney disease, characterized by elevated levels of urea and cyanate in the circulation and a possible increased risk of atherosclerosis. 9,24,25 It has also recently been shown that eosinophil peroxidase-mediated carbamylation of proteins can alter immune responses and give rise to a triggering of inflammatory signals in a similar way as could be seen in asthma. 26 Furthermore, cyanates could react with, and covalently bind to, glutathione which is a major lung antioxidant that plays an important role for reducing oxidative stress and airway inflammation.…”

Section: Concentration Of Ica Mic and Hcn In Frying Fumes (μG/m 3 ) Bmentioning

confidence: 96%

Isocyanates and hydrogen cyanide in fumes from heated proteins and protein‐rich foods

Leanderson

2018

Indoor Air

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Toxic compounds in cooking fumes could cause respiratory problems. In the present study, the formation of isocyanic acid (ICA), methyl isocyanate (MIC), and hydrogen cyanide (HCN) was studied during the heating of proteins or frying of protein‐rich foods. Heating was performed in an experimental setup using a tube oven set at 200‐500°C and in a kitchen when foods with different protein content were fried at a temperature around 300°C. ICA, MIC, and HCN were all generated when protein or meat was heated. Individual amino acids were also heated, and there was a significant positive correlation between their respective nitrogen content and the formation of the measured compounds. Gas from heated protein or meat also caused carbamylation in albumin. ICA, MIC, and HCN were also present in fumes generated when meat, egg, and halloumi were fried in a kitchen pan. The levels of ICA were here twice that of the Swedish occupational exposure limit. If ICA, MIC, and HCN in fumes from heated protein‐rich foods could contribute to the risk of airway dysfunction among those exposed is not clear, but it is important to avoid inhaling frying and grilling fumes and to equip kitchens with good exhaust ventilation.

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Emerging role of post-translational modifications in chronic kidney disease and cardiovascular disease

Cited by 88 publications

References 96 publications

The systemic nature of CKD

The systemic nature of CKD

Carbamylated Low-Density Lipoprotein (cLDL)-Mediated Induction of Autophagy and Its Role in Endothelial Cell Injury

Isocyanates and hydrogen cyanide in fumes from heated proteins and protein‐rich foods

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