Protein Oxidation Research Articles

Storage causes protein oxidation of soybean meal and affects antioxidant status, digestive performance and meat quality of broilers.

This study investigated the protein oxidation of soybean meal (SBM) stored in a warehouse and the effects of SBM on growth performance, antioxidant status, digestive performance, intestinal morphology, and breast muscle quality of broilers. In total, 160 one-day-old Arbor Acres Plus broilers (half male and half female) were randomly divided into two groups with ten replicates of eight birds each: The control group was served with a basal diet including SBM stored at -20°C (FSBM), and the experimental group was served with a basal diet including SBM stored in a warehouse at room temperature for 45 days (RSBM). Compared with FSBM, the protein carbonyl level in RSBM was increased, the free and total thiol levels and in vitro digestibility of protein were decreased. The RSBM decreased the serum glutathione (GSH) level and the hepatic total superoxide dismutase (T-SOD) activity at days 21 and 42 when compared with FSBM. Further, RSBM reduced the duodenal T-SOD activity, jejunal catalase (CAT), and T-SOD activities at day 21, and decreased the duodenal CAT and T-SOD activities, jejunal T-SOD activity, and ileal GSH level and T-SOD activity at days 21 and 42 when compared with FSBM. Besides, the trypsin activity and the ratio of villus height to crypt depth in small intestines of broilers at days 21 and 42 were reduced when fed with a RSBM-contained diet. Compared with FSBM, the 24-h drip loss, shear force, and 24- and 48-h cooking loss of breast muscle were increased of RSBM group, the opposite result was observed for muscle lightness at 48 h. Room temperature storage for 45 days led a protein oxidation and decreased in vitro digestibility in SBM, and fed RSBM impaired growth performance, antioxidant status, and meat quality, reduced trypsin activity, and affected the small intestine morphology in broilers.

Exploring the ameliorative potential of rutin against High-Sucrose Diet-induced oxidative stress and reproductive toxicity in Drosophila melanogaster

Sucrose is a vital ingredient in numerous food items consumed regularly. However, exposure to excessive sucrose for a prolonged period can promote health issues. The reproductive system has a delicate physiology that can be targeted by various chemical stressors, including sucrose. Hence, the present in vivo study aims to unveil the impacts of the High-Sucrose Diet (HSD) on the reproductive fitness of Drosophila melanogaster. In addition, the present work has also assessed the protective potential of a bioactive compound, rutin, against it. Here, 1st instar larvae were exposed to HSD (30%) alone and in combination with rutin (100-300µM) till their adult stage. HSD disturbed sex comb morphology in adult males, while fecundity and hatchability of eggs in females. Moreover, HSD triggered gonadal ROS production, oxidative stress, and modulated endogenous antioxidants such as SOD, catalase, and glutathione in both sexes. Nuclear fragmentation and tissue injuries, along with protein and lipid oxidation, were also apparent. Elevated levels of cytosolic Iron suggested an active Fenton reaction in adults. Further, HSD modulated the activities of reproductive and metabolic mediators, including vitellogenin, malate dehydrogenase, glucose-6-phosphate dehydrogenase, and angiotensin-converting enzymes that are critical to overall reproductive fitness. Interestingly, co-treatment with rutin, mainly at 200µM, mitigated these adverse effects and restored reproductive fitness. The protective potential of rutin might be attributed to its ability to normalize redox homeostasis, reduce oxidative stress, and optimize critical enzymes involved in reproductive physiology. These findings suggest that rutin has potential therapeutic implications to counteract the reproductive hazards induced by HSD.

Beyond glucose: The crucial role of redox signaling in β-cell metabolic adaptation

ObjectiveRedox signaling mediated by reversible oxidative cysteine thiol modifications is crucial for driving cellular adaptation to dynamic environmental changes, maintaining homeostasis, and ensuring proper function. This is particularly critical in pancreatic β-cells, which are highly metabolically active and play a specialized role in whole organism glucose homeostasis. Glucose stimulation in β-cells triggers signals leading to insulin secretion, including changes in ATP/ADP ratio and intracellular calcium levels. Additionally, lipid metabolism and reactive oxygen species (ROS) signaling are essential for β-cell function and health. MethodsWe employed IodoTMT isobaric labeling combined with tandem mass spectrometry to elucidate redox signaling pathways in pancreatic β-cells. ResultsGlucose stimulation significantly increases ROS levels in β-cells, leading to targeted reversible oxidation of proteins involved in key metabolic pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, pyruvate metabolism, oxidative phosphorylation, protein processing in the endoplasmic reticulum (ER), and insulin secretion. Furthermore, the glucose-induced increase in reversible cysteine oxidation correlates with the presence of other post-translational modifications, including acetylation and phosphorylation. ConclusionsProper functioning of pancreatic β-cell metabolism relies on fine-tuned regulation, achieved through a sophisticated system of diverse post-translational modifications that modulate protein functions. Our findings demonstrate that glucose induces the production of ROS in pancreatic β-cells, leading to targeted reversible oxidative modifications of proteins. Furthermore, protein activity is modulated by acetylation and phosphorylation, highlighting the complexity of the regulatory mechanisms in β-cell function.

Association of ambient ozone exposure with early cardiovascular damage among general urban adults: A repeated-measures cohort study in China

Longitudinal evidence of long-term ozone exposure on heart rate variability (HRV, an early indicator of cardiovascular damage) is lacking and the potential mechanism remains largely unclear. Our objectives were to evaluate the cross-sectional and longitudinal associations of ozone exposure with HRV alteration, and the potential roles of protein carbonyl (PC, biomarker of oxidative protein damage) and transforming growth factor (TGF)-β1 in this association. This repeated-measures prospective study included 4138 participants with 6617 observations from the Wuhan-Zhuhai cohort. Ozone concentrations were estimated using a high temporospatial resolution model for each participant. HRV indices, PC, and TGF-β1 were also repeatedly measured. Cross-sectional and longitudinal relationships of ozone exposure with HRV alteration were evaluated by linear mixed model. Cross-sectionally, the strongest lag effect of each 10 ppb increment in short-term ozone exposure showed a 12.40 %, 8.47 %, 4.31 %, 8.03 %, 3.69 %, and 2.41 % decrement on very low frequency (VLF, lag 3 weeks), LF (lag 2 weeks), high frequency (HF, lag 0–7 days), total power (TP, lag 2 weeks), standard deviation of all normal-to-normal intervals (SDNN, lag 3 weeks), and square root of the mean squared difference between adjacent normal-to-normal intervals (lag 2 weeks), respectively. Longitudinally, each 10 ppb increment of annual average ozone was related with an annual change rate of −0.024 ms2/year in VLF, −0.009 ms2/year in LF, −0.013 ms2/year in HF, −0.014 ms2/year in TP, and −0.004 ms/year in SDNN. Mediation analyses indicated that PC mediated 20.77 % and 12.18 % of ozone-associated VLF and TP decline, respectively; TGF-β1 mediated 16.87 % and 27.78 % of ozone-associated VLF and SDNN reduction, respectively. Our study demonstrated that ozone exposure was cross-sectionally and longitudinally related with HRV decline in general Chinese urban adults, and oxidative protein damage and increased TGF-β1 partly mediated ozone exposure-related HRV reduction.

Jerked beef as an ultraprocessed convenience food: Desalting strategies to minimize the impact on lipid and protein oxidation

AbstractJerked beef (JB) is a high‐protein convenience food but shows high degree of oxidation owing to its severe ultraprocessing. This study aimed to investigate the effect of desalting processes on oxidative stability of JB. JB were submitted to five desalting procedures: immersion in water at room temperature for 12 h without changing the water (AT12); immersion in water at room temperature for 12 h followed by boiling for 30 min and changing the water between the two procedures (AT12 + C30); immersion in boiled water for 10, 20, and 30 min (C10, C20, and C30, respectively). The desalted JB samples were refrigerated (vacuum packed and stored at 1 ± 1°C) and analyzed at 0 and 60 days. The samples without desalting were used as a control group. AT12 samples had the lowest lipid oxidation (0.05 and 0.07 mg of MDA kg−1, at T60 and T0, respectively). AT12 + C30 had the lowest NaCl content (2.8 and 3.3 g 100 g−1, at T0 and T60, respectively). C10, C20, and C30 showed a lower level of total carbonyls (p < 0.05) (0.04–0.13 nmol mg−1 protein), compared to control (0.53–0.93 nmol mg−1 protein in T0 and T60, respectively). Only boiled, desalted meats showed the volatile compound benzaldehyde. Higher concentration of monounsaturated, polyunsaturated, and total unsaturated fatty acids in JB desalted only in boiling water (C10, C20, and C30), compared to control (p < 0.05). AT12 is the best process to use, with regards to lipid oxidative stability, hardness, and NaCl content. Therefore, we conclude that it is possible to offer commercially desalted JB, as a convenience ultraprocessed product.Practical ApplicationLipid oxidation is accelerated when desalting jerked beef (JB) with boiling water. Desalted JB in boiling water had detectable concentrations of benzaldehyde. •Desalting in water at 25°C/12 h resulted in JB with better oxidative stability.

Benefits of Astaxanthin supplementation: selected issues

INTRODUCTION: Astaxanthin, a carotenoid compound belonging to the xanthophyll group, occurs naturally in algae, yeast, and marine organisms such as shrimp, trout, lobster, and krill. Renowned for its antioxidant prowess, astaxanthin shields mitochondria from harm caused by reactive oxygen species (ROS). Its exceptional antioxidant potency is noteworthy, surpassing that of α-tocopherol (Vitamin E) by 100-fold and eclipsing over 600 other recognized natural carotenoids. REVIEW METHODS: The article was complied by analyzing data from PubMed and Google Scholar data regarding the benefits of astaxanthin supplementation. THE STATE OF KNOWLEDGE: Astaxanthin, offers a range of health benefits. It modulates immune responses, inhibits cancer cell growth, reduces bacterial presence and gastric inflammation. With potent antioxidant properties, it also serves as a neuroprotective agent by combating neuroinflammation. Additionally, astaxanthin shows promise in preventing and treating liver diseases, thanks to its antioxidant, anti-inflammatory, and signaling pathway regulation properties. Overall, antioxidants like astaxanthin, whether from diet or supplements, help combat lipid and protein oxidation, thereby slowing down the progression of atherosclerosis. CONCLUSION: Astaxanthin emerges as a promising candidate for treating various pathological conditions linked to oxidative damage and impaired mitochondria function. These conditions span across cardiovascular diseases, neurodegenerative disorders and liver diseases. It could also help healthy people like athletes in enhancement of overall quality of life.

A glutamine metabolic switch supports erythropoiesis.

Metabolic requirements vary during development, and our understanding of how metabolic activity influences cell specialization is incomplete. Here, we describe a switch from glutamine catabolism to synthesis required for erythroid cell maturation. Glutamine synthetase (GS), one of the oldest functioning genes in evolution, is activated during erythroid maturation to detoxify ammonium generated from heme biosynthesis, which is up-regulated to support hemoglobin production. Loss of GS in mouse erythroid precursors caused ammonium accumulation and oxidative stress, impairing erythroid maturation and recovery from anemia. In β-thalassemia, GS activity is inhibited by protein oxidation, leading to glutamate and ammonium accumulation, whereas enhancing GS activity alleviates the metabolic and pathological defects. Our findings identify an evolutionarily conserved metabolic adaptation that could potentially be leveraged to treat common red blood cell disorders.

EPA or DHA enhanced oxidative stress and aging protein expression in brain of d-galactose treated mice

EPA or DHA enhanced oxidative stress and aging protein expression in brain of d-galactose treated mice

Influence of Chitosan/Lycopene on Myoglobin and Meat Quality of Beef During Storage

Myoglobin (Mb) is easily oxidized, which causes the discoloration of meat. In addition, various microorganisms are responsible for meat spoilage. Chitosan and lycopene can be used to protect the color and extend the shelf life of meat. In this study, a series of coatings with different ratios (1:0, 3:1, 1:1, 1:3, 0:1) of chitosan to lycopene were prepared. Beef was treated with different coatings. The changes in color, relative content of different Mb forms, thiobarbituric acid-reactive substances (TBARS), sulfhydryl content, carbonyl content, microbial count, cooking loss, and sensory evaluation during storage were investigated. The results showed that after 8 days, compared to the control, the relative content of oxymyoglobin (OxyMb), the lightness (L*) value, the redness (a*) value, and the composite index (CI) value of beef treated with chitosan/lycopene of 1:3 (w:w, the concentration of lycopene was 0.75% (w:v)) increased by 6.34%, 34.73%, 67.25%, and 116.27%, respectively. Meanwhile, the relative content of metmyoglobin (MetMb) and the yellowness (b*) value decreased by 11.67% and 23.21%, respectively. Additionally, beef treated with chitosan/lycopene of 1:3 also performed well in protein oxidation, fat oxidation, microbial count, and cooking loss. Generally, the beef treated with chitosan/lycopene of 1:3 showed the best comprehensive quality. The coating was suitable for application in beef. These results are promising for food preservation.

Protective role of short-chain fatty acids on intestinal oxidative stress induced by TNF-α.

Inflammatory bowel diseases (IBD) are driven by an exaggerated inflammatory response, which leads to a marked increase in oxidative stress. This, in turn, exacerbates the inflammatory process and causes significant cellular and tissue damage. Intestinal dysbiosis, a common observation in IBD patients, alters the production of bacterial metabolites, including short-chain fatty acids (SCFAs), which are key by-products of dietary fiber fermentation. While the role of SCFAs in intestinal physiology is still being elucidated, this study aimed to investigate their effects on intestinal oxidative stress, particularly under inflammatory conditions induced by the proinflammatory mediator tumour necrosis factor alpha (TNF-α). The Caco-2/TC7 cell line was employed as an in vitro model of the intestinal epithelium, and the cells were treated with a range of SCFAs, including acetate, propionate, and butyrate. The levels of protein and lipid oxidation were quantified, as well as the activity of antioxidant enzymes. Our findings demonstrate that microbiota-derived SCFAs can effectively mitigate TNF-α-induced oxidative stress by modulating antioxidant enzyme activity. The proinflammatory mediator TNF-α induces lipid peroxidation by inhibiting catalase and glutathione peroxidase activities. SCFAs are able to upregulate antioxidant enzyme activity to restore lipid oxidative levels. These results underscore the critical role of the gut microbiota in maintaining intestinal homeostasis and highlight the therapeutic potential of SCFAs in managing oxidative stress-related pathologies.

Copper homeostasis and neurodegenerative diseases

Copper, one of the most prolific transition metals in the body, required for normal brain physiological activity and allows various functions to work normally through its range of concentrations. Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins, including copper transporters (CTR1 and CTR2), the two copper ion transporters the Cu -transporting ATPase 1 (ATP7A) and Cu-transporting beta (ATP7B), and the three copper chaperones ATOX1, CCS, and COX17. Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue. Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins, including ceruloplasmin and metallothionein, is involved in the pathogenesis of neurodegenerative disorders. However, the exact mechanisms underlying these processes are not known. Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress. Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction. Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation, with elevated levels activating several critical inflammatory pathways. Additionally, copper can bind aberrantly to several neuronal proteins, including alpha-synuclein, tau, superoxide dismutase 1, and huntingtin, thereby inducing neurotoxicity and ultimately cell death. This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases, with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis. By synthesizing the current findings on the functions of copper in oxidative stress, neuroinflammation, mitochondrial dysfunction, and protein misfolding, we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders, such as Wilson's disease, Menkes' disease, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Potential clinically significant therapeutic targets, including superoxide dismutase 1, D-penicillamine (DPA), and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline (PBT2), along with their associated therapeutic agents, are further discussed. Ultimately, we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.

Mitochondria-Targeted DNA Repair Glycosylase hOGG1 Protects Against HFD-Induced Liver Oxidative Mitochondrial DNA Damage and Insulin Resistance in OGG1-Deficient Mice

8-oxoguanine DNA glycosylase-1 (OGG1) is a DNA glycosylase mediating the first step in base excision repair which removes 7,8-dihydro-8-oxoguanine (8-oxoG) and repairs oxidized nuclear and mitochondrial DNA. Previous studies showed that OGG1 deficiency results in an increased susceptibility to high-fat diet (HFD)-induced obesity and metabolic dysfunction in mice, suggesting a crucial role of OGG1 in metabolism. However, the tissue-specific mechanisms of how OGG1 deficiency leads to insulin resistance is unknown. Thus, in the current study, we used a hyperinsulinemic-euglycemic clamp to evaluate in-depth glucose metabolism in male wild-type (WT) mice and Ogg1−/− (Ogg1-KO) mice fed an HFD. Ogg1-KO mice fed HFD were more obese, with significantly lower hepatic insulin action compared to WT/HFD mice. Targeting human OGG1 to mitochondria protected against HFD-induced obesity, insulin resistance, oxidative mitochondrial DNA damage in the liver and showed decreased expression of liver gluconeogenic genes in Ogg1-KO mice, suggesting a putative protective mechanism. Additionally, several subunits of oxidative phosphorylation protein levels were noticeably increased in Ogg1-KO/Tg compared to Ogg1-KO mice fed an HFD which was associated with improved insulin signaling. Our findings demonstrate the crucial role of mitochondrial hOGG1 in HFD-induced insulin resistance and propose several protective mechanisms which can further direct the development of therapeutic treatment.

Phytochemicals in Parkinson's Disease: a Pathway to Neuroprotection and Personalized Medicine.

Parkinson's disease (PD) is a complex neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the substantia nigra. While current treatments primarily manage symptoms, there is increasing interest in alternative approaches, particularly the use of phytochemicals from medicinal plants. These natural compounds have demonstrated promising neuroprotective potential in preclinical studies by targeting key pathological mechanisms such as oxidative stress, neuroinflammation, and protein aggregation. However, the clinical translation of these phytochemicals is limited due to a lack of robust clinical trials evaluating their safety, efficacy, and pharmacokinetics. This review provides a comprehensive overview of the neuroprotective potential of phytochemicals in PD management, examining the mechanisms underlying PD pathogenesis and emphasizing neuroprotection. It explores the historical and current research on medicinal plants like Mucuna pruriens, Curcuma longa, and Ginkgo biloba, and discusses the challenges in clinical translation, including ethical and practical considerations and the integration with conventional therapies. It further underscores the need for future research to elucidate mechanisms of action, optimize drug delivery, and conduct rigorous clinical trials to establish the safety and efficacy of phytochemicals, aiming to shape future neuroprotective strategies and develop more effective, personalized treatments for PD.

TMET-31. OXIDATIVE STRESS INDUCED PROTEIN AGGREGATION VIA GGCT PRODUCED PYROGLUTAMIC ACID IN DRUG RESISTANT GLIOBLASTOMA

Abstract Drug resistance is a major barrier to cancer therapies and remains poorly understood. Recently, non-mutational mechanisms of drug resistance have been proposed where a more plastic metabolic response can play a major role. Here, we show that upon drug resistance, glioblastoma (GBM) cells have increased oxidative stress, mitochondria function, and protein aggregation. Gamma (y)-glutamylcyclotranserase (GGCT), an enzyme in the y-glutamyl cycle for glutathione production, located on chromosome 7 which is commonly amplified in GBM is also increased upon resistance. We further observe that the byproduct of GGCT – pyroglutamic acid – can bind aggregating proteins and that genetic and pharmacological inhibition of GGCT prevents protein aggregation. Finally, we found increased protein aggregation, GGCT expression, and pyroglutamic acid staining in recurrent GBM patient samples, as well as adjacent normal brain. These findings suggest a new pathway for protein aggregation within drug resistant brain cancer that should be further studied in other brain disorders.

INDICATORS OF FREE RADICAL OXIDATION AND ANTIOXIDANT PROTECTION IN THE ORAL FLUID OF CHILDREN WITH CHRONIC CATARRHAL GINGIVITIS AND DIABETIS MELLITUS

Failure of antioxidant mechanisms leads to an increase in lipid peroxidation products in the body, resulting in a non-specific cascade of cellular membrane damage. Proteins play a crucial role in metabolic processes, but when lipid peroxidation intensifies, protein modifications occur, leading to fragmentation, denaturation, and loss of biological activity. This disruption impairs tissue regenerative processes. The objective of this study was to analyze indicators of free radical oxidation and antioxidant protection in the oral fluid of children with chronic catarrhal gingivitis and type I diabetes mellitus. Materials and methods. A total of 170 children aged 12 to 16 were observed, including 130 who were examined and treated at the Endocrinology Department of the Regional Municipal Non-Profit Institution “Chernivtsi Regional Pediatric Clinical Hospital” for type 1 diabetes mellitus. Among them, 74 children had a disease duration of less than 5 years, including 65 with chronic catarrhal gingivitis. Sixty five children had diabetes for more than 5 years, with 44 of them diagnosed to have chronic catarrhal gingivitis. The children with chronic catarrhal gingivitis were further divided into groups based on their level of glycemic control: 1 child with optimal glycemic control, 66 with suboptimal glycemic control, and 42 with glycemic control at a high risk to life. The control group included 40 practically healthy children: 22 of them had clinically healthy periodontal tissues, and 18 children were diagnosed to suffer from chronic catarrhal gingivitis. Results. The study performed found out that children with chronic catarrhal gingivitis present increased indicators of lipid peroxide oxidation (protein oxidative modification, diene conjugates, malondialdehyde) and decreased activity of the enzyme in the antioxidant protective system of the oral fluid (whole protein, НS-groups, ceruloplasmin, activity of supermutase and catalase) in comparison with indicators of children without dental pathology. The most considerable changes were found in patients with chronic catarrhal gingivitis and type 1 diabetes mellitus, especially when the disease lasted more than 5 years (р<0,05).

Mass Spectrometry-Based Platforms for Protein Lipoxidation Profiling.

Lipid peroxidation, occurring through enzymatic or non-enzymatic processes, generates lipid-derived electrophiles (LDEs), which can covalently modify nucleophilic amino acid residues in proteins, a process known as protein lipoxidation. This modification can alter protein structure and function, either causing damage or regulating signalling pathways. Identifying the protein targets and specific lipoxidation sites provide important clues for unveiling the oxidative stress-related protein interaction network and molecular mechanisms of related diseases. In this review, we present a detailed overview of recent advances in protein LDE modification profiling, with a focus on mass spectrometry (MS)-based chemoproteomic platforms for global protein lipoxidation profiling.

Discovery of Thiazole Carboxamides as Novel Vanin-1 Inhibitors for Inflammatory Bowel Disease Treatment.

Inflammatory bowel disease (IBD) is a clinically heterogeneous disease demanding more therapeutic targets and intervention strategies. Vanin-1, an oxidative stress-regulating protein, has emerged as a promising target for alleviating inflammation and oxidative stress. In this study, a series of thiazole carboxamide derivatives as vanin-1 inhibitors were designed and synthesized. The preferred compound, X17, demonstrated potent inhibition against vanin-1 at the protein, HT-29 cell, and tissue levels, whose binding mode with the target was confirmed via the cocrystal structure. X17 achieved a high bioavailability of 81% in rats, accompanied by concentration-dependent inhibition of serum vanin-1. In a DSS-induced mouse colitis model, X17 exhibited potent anti-inflammatory and antioxidant activities, repressing the inflammatory factor expressions and myeloperoxidase activity, elevating the colonic glutathione reserve, and restoring the intestinal barrier. Collectively, these findings depict the discovery of a potent vanin-1 inhibitor, providing an opportunity for further drug candidate development for treating IBD.

High dose of liraglutide impairs renal function in female hypertensive rats.

Glucagon-like peptide-1 (GLP-1) receptor agonists exhibit beneficial cardiovascular effects. However, the renal effects of different doses of liraglutide in an essential hypertension model have not yet been investigated. SHR female rats were treated for 30 days, twice a day, with saline (control) or liraglutide at low (0.06 mg/kg, LL) and high (0.6 mg/kg, LH) doses. Volume intake and excretion were monitored for a period of 24h. In renal tissue, nitrite-NO2-, nitrate-NO3-, advanced protein oxidation products-AOPP, collagen deposition, creatinine (Cr), urea (U), sodium, and potassium were analyzed. liraglutide reduced body weight gain in both groups. However, in the high dose, it increased urinary volume excretion and sodium/potassium ratio. Both doses reduced the urinary U/Cr ratio and LH increased the serum U/Cr ratio. AOPP was reduced only in LL. LH augmented collagen and early markers of kidney injury (blood urea nitrogen-BUN, BUN/Cr). LH increased NO3-, reduced NO2-, and caused an aberrant increase in GFR. Both doses' effects were independent of blood pressure and glycemic control. liraglutide appears to have distinct effects on the hypertensive female kidney depending on the dose, with higher doses impairing kidney function.

Differential contribution of Cu2+ and OH− to the formation of Nε-carboxymethyllysine and Nε-carboxyethyllysine in preserved egg white during pickling

In this study, the relationship between advanced glycosylation end products (AGEs) in preserved egg white (PEW) with protein oxidation and precursors induced by OH− and Cu2+ were performed to clarify the differential contribution of OH− and Cu2+ on the formation of AGEs during pickling. It was found that AGEs were more easily formed in PEW rather than yolk, and the accumulation of Nε-carboxymethyllysine (CML) could be promoted through protein oxidation related to carbonyl compounds, tryptophan induced by Cu2+ at early stage, while carbonyl compounds were more conducive to form Nε-carboxyethyllysine (CEL) under synergistic action of Cu2+ and OH−. At later period, Schiff base promoted the formation of CEL and CML in the presence of Cu2+. Meanwhile, the enrichment of CEL and CML could both be promoted by α-dicarbonyl compounds in presence of Cu2+ and/or OH−. This manuscript will provide theoretical guidance for reducing and limiting hazardous compounds in preserved eggs.

EIF5A controls mitoprotein import by relieving ribosome stalling at TIM50 translocase mRNA.

Efficient import of nuclear-encoded proteins into mitochondria is crucial for proper mitochondrial function. The conserved translation factor eIF5A binds ribosomes, alleviating stalling at polyproline-encoding sequences. eIF5A impacts mitochondrial function across species, though the precise molecular mechanism is unclear. We found that eIF5A depletion in yeast reduces the translation and levels of the TCA cycle and oxidative phosphorylation proteins. Loss of eIF5A causes mitoprotein precursors to accumulate in the cytosol and triggers a mitochondrial import stress response. We identify an essential polyproline protein as a direct target of eIF5A: the mitochondrial inner membrane protein and translocase component Tim50. Thus, eIF5A controls mitochondrial protein import by alleviating ribosome stalling along Tim50 mRNA at the mitochondrial surface. Removal of polyprolines from Tim50 partially rescues the mitochondrial import stress response and translation of oxidative phosphorylation genes. Overall, our findings elucidate how eIF5A impacts the mitochondrial function by promoting efficient translation and reducing ribosome stalling of co-translationally imported proteins, thereby positively impacting the mitochondrial import process.