Hyperglycemia induced reactive species trigger structural changes in human serum albumin of type 1 diabetic subjects

Arif, Zarina; Neelofar, Km; Arfat, Mir Yasir; Zaman, Asif; Tarannum, Akhlas; Parveen, Iffat; Ahmad, Shafeeque; Khan, Adnan; Badar, Asim; Islam, Shireen Naaz

doi:10.1016/j.ijbiomac.2017.10.091

Cited by 7 publications

(4 citation statements)

References 58 publications

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“…Protein carbonylation determination has long been used to assess the degree of oxidative stress in a variety of diseases including Alzheimer’s disease, chronic lung disease, chronic renal failure, diabetes, sepsis, amyotrophic lateral sclerosis, cataractogenesis, cystic fibrosis, rheumatoid arthritis, and ischemia-reperfusion injury. − Because of its abundance and nucleophilic residues, which can interact with α,β-unsaturated aldehydes such as acrolein, carbonylated albumin has been investigated as a biomarker of oxidative stress in uremia, liver disease, stroke, and diabetes. − While acrolein interaction with cytoskeletal proteins and enzymes has been implicated in cell and tissue damage, − the causative or consequential contribution of acrolein-mediated albumin carbonylation in disease onset and/or progression is unclear.…”

Section: Discussionmentioning

confidence: 99%

Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts

Bein

Birru

Wells

et al. 2020

Chem. Res. Toxicol.

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Albumin is an abundant protein in the lung lining fluid that forms an interface between lung epithelial cells and the external environment. In the lung, albumin can be targeted for adduction by inhaled acrolein. Acrolein, an α,β-unsaturated aldehyde, reacts with biomolecules via Michael addition at the β-carbon or Schiff base formation at the carbonyl carbon. To gain insight into acrolein's mode of action, we investigated in vitro albumin−acrolein reactivity and the consequence of albumin adduction by acrolein on cytotoxicity and transcript changes in NCI-H441 and human airway epithelial cells (HAEC). Albumin protected NCI-H441 cells from acrolein toxicity. In addition, albumin inhibited acrolein-induced increase of transcripts associated with cellular stress response, activating transcription factor 3 (ATF3), and antioxidant response, heme oxygenase 1 (HMOX1) in HAEC cells. Acrolein-adducted albumin itself increased HMOX1 transcripts but not ATF3 transcripts. The HMOX1 transcript increase was inhibited by hydralazine, a carbonyl scavenger, suggesting that the carbonyl group of acroleinadducted albumin mediated HMOX1 transcript increase. In acutely exposed C57BL/6J mice, bronchoalveolar lavage protein carbonylation increased. Acrolein-adducted albumin Cys34 was identified by nLC-MS/MS. These findings indicate that adduction of albumin by acrolein confers a cytoprotective function by scavenging free acrolein, decreasing a cellular stress response, and inducing an antioxidant gene response. Further, these results suggest that β-carbon reactivity may be required for acrolein's cytotoxicity and ATF3 transcript increase, and the carbonyl group of acrolein-adducted albumin can induce HMOX1 transcript increase.

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Section: Discussionmentioning

confidence: 99%

Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts

Bein

Birru

Wells

et al. 2020

Chem. Res. Toxicol.

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“…Both ROS and AGEs can impair β-cell function, advancing to T1D development. Hyperglycemia induces oxido-nitrosative stress in T1D, producing immunologically active human serum albumin (HSA), presumably through glycation-induced oxidation [ 22 ].…”

Section: Ptms In Type 1 Diabetesmentioning

confidence: 99%

Post-Translational Modifications and Diabetes

Sharma,

Hamza,

Boyle

et al. 2024

Biomolecules

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Diabetes and its associated complications have increasingly become major challenges for global healthcare. The current therapeutic strategies involve insulin replacement therapy for type 1 diabetes (T1D) and small-molecule drugs for type 2 diabetes (T2D). Despite these advances, the complex nature of diabetes necessitates innovative clinical interventions for effective treatment and complication prevention. Accumulative evidence suggests that protein post-translational modifications (PTMs), including glycosylation, phosphorylation, acetylation, and SUMOylation, play important roles in diabetes and its pathological consequences. Therefore, the investigation of these PTMs not only sheds important light on the mechanistic regulation of diabetes but also opens new avenues for targeted therapies. Here, we offer a comprehensive overview of the role of several PTMs in diabetes, focusing on the most recent advances in understanding their functions and regulatory mechanisms. Additionally, we summarize the pharmacological interventions targeting PTMs that have advanced into clinical trials for the treatment of diabetes. Current challenges and future perspectives are also provided.

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“…The persistent hyperglycemic state observed in diabetic patients is the main source of carbonylation compounds, which are precursors of AGEs, presumably responsible for the significant increase in AGEs in patients with diabetes [83]. On the one hand, AGEs promote non-enzymatic cross-linking of collagen molecules, destroy the bone structure, reduce the biomechanical quality of bones, and ultimately lead to bone embrittlement [20,28,29,34,35].…”

Section: Risk Of Fracture In Patients With Diabetesmentioning

confidence: 99%

Advanced Glycation End Products, Bone Health, and Diabetes Mellitus

Jiang

Zhao

Han

et al. 2022

Exp Clin Endocrinol Diabetes

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Advanced glycation end products (AGEs), the compounds resulting from the non-enzymatic glycosylation between reducing sugars and proteins, are derived from food or produced de novo. Over time, more and more endogenous and exogenous AGEs accumulate in various organs such as the liver, kidneys, muscle, and bone, threatening human health. Among these organs, bone is most widely reported. AGEs accumulating in bone reduce bone strength by participating in bone structure formation and breaking bone homeostasis by binding their receptors to alter the proliferation, differentiation, and apoptosis of cells involved in bone remodeling. In this review, we summarize the research about the effects of AGEs on bone health and highlight their associations with bone health in diabetes patients to provide some clues toward the discovery of new treatment and prevention strategies for bone-related diseases caused by AGEs.

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Hyperglycemia induced reactive species trigger structural changes in human serum albumin of type 1 diabetic subjects

Cited by 7 publications

References 58 publications

Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts

Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts

Post-Translational Modifications and Diabetes

Advanced Glycation End Products, Bone Health, and Diabetes Mellitus

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