Biophysical changes in methylglyoxal modified fibrinogen and its role in the immunopathology of type 2 diabetes mellitus

Perween, Shahida; Abidi, Minhal; Faizy, Abul Faiz; Moinuddin, Mohammed

doi:10.1016/j.ijbiomac.2021.12.161

Cited by 6 publications

(2 citation statements)

References 80 publications

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“…Methylglyoxal, a precursor of APMD, induces cell cycle arrest at G0/G1 phase (Milanesa et al, 2000). Although the tertiary structure of fibrinogen is modified by methylglyoxal through glycosylation to form APMD (Perween et al, 2022), our data found that APMD could still induce an increase in the proportion of cells in the G0/G1 phase, which provides a new insight into the relationship between cell cycle and methylglyoxal derivative. Cyclin D1/CDK complex activation triggers cells to enter the S phase from G1.…”

Section: Discussionmentioning

confidence: 57%

Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction

Dong

Gao

et al. 2022

Journal Cellular Physiology

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Argpyrimidine (APMD), a methylglyoxal-arginine-derived product, is one of the main products of diabetes mellitus. We aimed to systematically investigate the role of APMD in regulating autophagy activity, with a specific focus on the finding of APDM binding molecule, matching amino acid residues, autophagy flux and proteins, cell cycle arrest, cell skeleton and migration, PI3K/AKT/mTOR pathways, inflammatory signals, alveolar bone destruction, and inhibition verification. In this study, binding to 59/94/121 amino acid residues of advanced glycosylation end product receptor (RAGE), APMD suppressed PI3K/AKT/mTOR pathway to attenuate cell survival of periodontal ligament cells (PDLCs). Simultaneously, autophagy proteins ATG5, Beclin1, and LC3-II/I expression ratio were upregulated while P62/SQSTM was downregulated. Cell cycle arrested at G0/G1 with enhancing Cyclin D1/CDK4 and decreasing Cyclin A/CDK2 expression. Inhibition of autophagy abrogated APMDinduced cell cycle arrest. Furthermore, the inflammation regulation network of matrix metalloproteinase (MMP)-2, MMP-9, MAPKs and NF-κB pathways were activated by APMD. Rat periodontal models confirmed that APMD induced alveolar bone resorption, increased inflammatory infiltrates, and degraded collagen fibers through RAGE and PI3K. APMD-induced autophagy, G0/G1 arrest, proinflammatory signals activating and periodontal destruction were reversed by RAGE knockdown while aggravated by PI3K inhibitor. This study provides the first evidence that APMD bind to RAGE to regulate autophagy and cell cycle of PDLCs through the PI3K/AKT/mTOR pathway, thereby promoting periodontal destruction.

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Section: Discussionmentioning

confidence: 57%

Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction

Dong

Gao

et al. 2022

Journal Cellular Physiology

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“…40–43 Most importantly, the disulfide bridges in proteins treated with methylglyoxal are susceptible to fragmentation, leading to protein unfolding. 44 The disulfide bond-cleaved unfolded protein chains can form compact, short-range-ordered β-sheets, followed by aggregation to form nanoscale β-sheet-rich amphiphilic oligomers without breaking any amide bonds in the protein backbone. 45–47 Han et al , 2020 demonstrated that these nanoscale oligomers could generate submicrometric spherical products through hydrophobic interactions.…”

Section: Resultsmentioning

confidence: 99%

Label-free visualization of unfolding and crosslinking mediated protein aggregation in nonenzymatically glycated proteins

Mukunda,

Basha,

D'Souza

et al. 2024

Analyst

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Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis

Patil,

Tupe

2023

Medicinal Research Reviews

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Diabetes and its complications, Alzheimer's disease (AD), and Parkinson's disease (PD) are increasing gradually, reflecting a global threat vis‐à‐vis expressing the essentiality of a substantial paradigm shift in research and remedial actions. Protein glycation is influenced by several factors, like time, temperature, pH, metal ions, and the half‐life of the protein. Surprisingly, most proteins associated with metabolic and neurodegenerative disorders are generally long‐lived and hence susceptible to glycation. Remarkably, proteins linked with diabetes, AD, and PD share this characteristic. This modulates protein's structure, aggregation tendency, and toxicity, highlighting renovated attention. Gut microbes and microbial metabolites marked their importance in human health and diseases. Though many scientific shreds of evidence are proposed for possible change and dysbiosis in gut flora in these diseases, very little is known about the mechanisms. Screening and unfolding their functionality in metabolic and neurodegenerative disorders is essential in hunting the gut treasure. Therefore, it is imperative to evaluate the role of glycation as a common link in diabetes and neurodegenerative diseases, which helps to clarify if modulation of nonenzymatic glycation may act as a beneficial therapeutic strategy and gut microbes/metabolites may answer some of the crucial questions. This review briefly emphasizes the common functional attributes of glycation and gut microbes, the possible linkages, and discusses current treatment options and therapeutic challenges.

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Biophysical changes in methylglyoxal modified fibrinogen and its role in the immunopathology of type 2 diabetes mellitus

Cited by 6 publications

References 80 publications

Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction

Argpyrimidine bonded to RAGE regulates autophagy and cell cycle to cause periodontal destruction

Label-free visualization of unfolding and crosslinking mediated protein aggregation in nonenzymatically glycated proteins

Communal interaction of glycation and gut microbes in diabetes mellitus, Alzheimer's disease, and Parkinson's disease pathogenesis

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