Homocysteine Modification in Protein Structure/Function and Human Disease

Jakubowski, Hieronim

doi:10.1152/physrev.00003.2018

Cited by 213 publications

(249 citation statements)

References 346 publications

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“…Hcy-thiolactone can contribute significantly to Hcy pools, particularly in urine. As suggested by Jakubowsky [22], Hcy-thiolactone has adverse effects on physiological function, underscoring the importance of examining urinary and plasma Hcy-thiolactone in addition to Hcy in the context of human disease. Modification by Hcy-thiolactone seems to explain Hcy toxicity in autoimmune response, cellular toxicity, and atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

Azzini

Ruggeri

Polito

2020

IJMS

106

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Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case–control experimental designs and the study of interactions between different factors it should be emphasized.

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Section: Introductionmentioning

confidence: 99%

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

Azzini

Ruggeri

Polito

2020

IJMS

106

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“…The concentration of Cys in the human body is determined by the level of N-acetyl-cysteine and also by the process called transsulfuration, in which homocysteine (Hcy) formed from the dietary methionine is transferred to Cys. The first step of transsulfuration is catalyzed by cystathionine β-synthase [16,17]. Hcy (Figure 1e), a type of amino acid that is naturally found in blood, is not harmful at normal levels.…”

Section: Introductionmentioning

confidence: 99%

A Simplified Method for Simultaneous Determination of α-Lipoic Acid and Low-Molecular-Mass Thiols in Human Plasma

Borowczyk

Olejarz

Chwatko

et al. 2020

IJMS

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α-Lipoic acid, glutathione, cysteine, and cysteinylglycine can be applied as therapeutic agents in civilization diseases such as diabetes mellitus, cardiovascular diseases, and cancers. On the other hand, a higher concentration of homocysteine can result in health problems and has been indicated as an independent risk factor for cardiovascular disease and accelerated atherosclerosis. Here, the first simplified HPLC-UV assay that enables simultaneous determination of α-lipoic acid and low-molecular-mass thiols in plasma, reduces the number of steps, shortens the total time of sample preparation, and limits the amount of single-use polypropylene laboratory materials is described. The assay is based on reversed-phase high performance liquid chromatography with UV detection and simultaneous reduction of disulfide bound with tris(2-carboxyethyl)phosphine and the selective pre-column derivatization of the thiol group with 1-benzyl-2-chloropyridinium bromide. Linearity in the detector responses for plasma samples were observed in ranges: 0.12–5.0 nmol mL−1 for α-lipoic acid; 2.0–20.0 nmol mL−1 for glutathione, cysteinylglycine, and homocysteine; and 40.0–400.0 for cysteine. The LODs for α-lipoic acid and low-molecular-mass thiols were 0.08 and 0.12 nmol mL−1, respectively, while LOQs were 0.12 and 0.16 nmol mL−1, respectively. The usefulness of the proposed method has been proven by its application to real samples.

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“…HHcy-induced kidney damage may be associated with multiple factors such as increased oxidative stress [8] and endoplasmic reticulum stress [9], inhibition of DNA methyl-ation [10], and homocysteine modification of protein [11]. Under physiological conditions, cells display a universal self-protective mechanism, namely, autophagy.…”

Section: Introductionmentioning

confidence: 99%

Nitrative Stress-Related Autophagic Insufficiency Participates in Hyperhomocysteinemia-Induced Renal Aging

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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The kidneys are important organs that are susceptible to aging. Hyperhomocysteinemia (HHcy) is a risk factor for nephropathy and is associated with chronic nephritis, purpuric nephritis, and nephrotic syndrome. Numerous studies have shown that elevated serum homocysteine levels can damage the kidneys; however, the underlying mechanism of HHcy on kidney damage remains unclear. In this study, we make use of a diet-induced HHcy rat model and in vitro cell culture to explore the role of autophagy in HHcy-induced renal aging and further explored the underlying mechanism. We demonstrated that HHcy led to the development of renal aging. Promoted kidney aging and autophagic insufficiency were involved in HHcy-induced renal aging. HHcy decreased the expression of transcription factor EB (TFEB), the key transcription factor of autophagy-related genes in renal tissue. Further experiments showed that nitrative stress levels were increased in the kidney of HHcy rats. Interestingly, pretreatment with the peroxynitrite (ONOO-) scavenger FeTMPyP not only reduced the Hcy-induced nitrative stress in vitro but also partially attenuated the decrease in TFEB in both protein and mRNA levels. Moreover, our results indicated that HHcy reduced TFEB expression and inhibited TFEB-mediated autophagy activation by elevating nitrative stress. In conclusion, this study showed an important role of autophagic insufficiency in HHcy-induced renal aging, in which downregulation of TFEB plays a major role. Furthermore, downexpression of TFEB was associated with increased nitrative stress in HHcy. This study provides a novel insight into the mechanism and therapeutic strategy for renal aging.

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Homocysteine Modification in Protein Structure/Function and Human Disease

Cited by 213 publications

References 346 publications

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

A Simplified Method for Simultaneous Determination of α-Lipoic Acid and Low-Molecular-Mass Thiols in Human Plasma

Nitrative Stress-Related Autophagic Insufficiency Participates in Hyperhomocysteinemia-Induced Renal Aging

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