Advanced glycation end products and their adverse effects: The role of autophagy

Sruthi, C R; Raghu, Kozhiparambil Gopalan

doi:10.1002/jbt.22710

Cited by 19 publications

(12 citation statements)

References 192 publications

(237 reference statements)

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“…These molecules are normally synthesized during metabolism, but they can also be uptaken from the diet: sugar-rich foods are considered the main exogenous source of AGEs, exerting a significant influence on the development of several pathological complications in diabetic patients [ 54 ]. AGEs interfere with the normal functioning of almost all body organs by exerting multiple actions such as apoptosis, inflammation, protein dysfunction, mitochondrial dysfunction, and oxidative stress [ 55 ]. Studies suggest that a diet low in AGEs has beneficial effects on insulin resistance and on fasting insulin, total cholesterol, and LDL levels [ 56 ].…”

Section: Main Findings and Discussionmentioning

confidence: 99%

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

Negrini

Carlos

Duque

et al. 2021

Front. Oral. Health

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This comprehensive review of the literature aimed to investigate the interplay between the oral microbiome, oral cavity conditions, and host immune response in Diabetes mellitus (DM). Moreover, this review also aimed to investigate how DM related risk factors, such as advanced age, hyperglycemia, hyperlipidemia, obesity, hypertension and polycystic ovary syndrome (PCOS), act in promoting or modifying specific mechanisms that could potentially perpetuate both altered systemic and oral conditions. We found that poorly controlled glycemic index may exert a negative effect on the immune system of affected individuals, leading to a deficient immune response or to an exacerbation of the inflammatory response exacerbating DM-related complications. Hyperglycemia induces alterations in the oral microbiome since poor glycemic control is associated with increased levels and frequencies of periodontal pathogens in the subgingival biofilm of individuals with DM. A bidirectional relationship between periodontal diseases and DM has been suggested: DM patients may have an exaggerated inflammatory response, poor repair and bone resorption that aggravates periodontal disease whereas the increased levels of systemic pro-inflammatory mediators found in individuals affected with periodontal disease exacerbates insulin resistance. SARS-CoV-2 infection may represent an aggravating factor for individuals with DM. Individuals with DM tend to have low salivary flow and a high prevalence of xerostomia, but the association between prevalence/experience of dental caries and DM is still unclear. DM has also been associated to the development of lesions in the oral mucosa, especially potentially malignant ones and those associated with fungal infections. Obesity plays an important role in the induction and progression of DM. Co-affected obese and DM individuals tend to present worse oral health conditions. A decrease in HDL and, an increase in triglycerides bloodstream levels seem to be associated with an increase on the load of periodontopathogens on oral cavity. Moreover, DM may increase the likelihood of halitosis. Prevalence of impaired taste perception and impaired smell recognition tend to be greater in DM patients. An important interplay among oral cavity microbiome, DM, obesity and hypertension has been proposed as the reduction of nitrate into nitrite, in addition to contribute to lowering of blood pressure, reduces oxidative stress and increases insulin secretion, being these effects desirable for the control of obesity and DM. Women with PCOS tend to present a distinct oral microbial composition and an elevated systemic response to selective members of this microbial community, but the association between oral microbiome, PCOS are DM is still unknown. The results of the studies presented in this review suggest the interplay among the oral microbiome, oral cavity conditions, host immune response and DM and some of the DM associated risk factors exist. DM individuals need to be encouraged and motivated for an adequate oral health care. In addition, these results show the importance of adopting multidisciplinary management of DM and of strengthening physicians-dentists relationship focusing on both systemic and on oral cavity conditions of DM patients.

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Section: Main Findings and Discussionmentioning

confidence: 99%

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

Negrini

Carlos

Duque

et al. 2021

Front. Oral. Health

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“…3 Prolonged hyperglycemia during diabetes is responsible for the nonenzymatic covalent adducts formation in the form of AGEs between reducing sugars and macromolecules like proteins, lipids, or nucleic acids. 4 One of the prime precursors for AGEs formation is methylglyoxal (MGO). 5 MGO is a highly reactive dicarbonyl metabolite, which can react with the lysine and arginine residues of proteins to form AGEs mostly hydroimidazolones adducts and argpyrimidines.…”

Section: Introductionmentioning

confidence: 99%

“…6 These can link with receptors of advanced glycation end products (RAGE) to stimulate several pathological signaling pathways. 4,7 The gradual accumulation of MGO has been linked with several agerelated diseases, 8 cardiovascular diseases (CVDs), Alzheimer's disease, and liver complications. 2,9 It is also implicated as an emerging biological factor in cancer development and progression.…”

Section: Introductionmentioning

confidence: 99%

“…Researchers nowadays have pointed out advanced glycation end products (AGEs) as one of the major players in diabetes and associated complications 3 . Prolonged hyperglycemia during diabetes is responsible for the nonenzymatic covalent adducts formation in the form of AGEs between reducing sugars and macromolecules like proteins, lipids, or nucleic acids 4 . One of the prime precursors for AGEs formation is methylglyoxal (MGO) 5 .…”

Section: Introductionmentioning

confidence: 99%

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Methylglyoxal induces ambience for cancer promotion in HepG2 cells via Warburg effect and promotes glycation

Sruthi

Raghu

2022

J of Cellular Biochemistry

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Methylglyoxal (MGO) is a toxic, highly reactive metabolite derived mainly from glucose and amino acids degradation. MGO is also one of the prime precursors for advanced glycation end products formation. The present research was performed to check whether MGO has any role in the promotion of cancer in HepG2 cells. For this, cells were incubated with MGO (50 µM) for 24 h and subjected to various analyses. Aminoguanidine (200 µM) was positive control. The various biochemical and protein expression studies, relevant to the MGO detoxification system, oxidative stress, and glycolysis were performed. MGO caused the reduction of expression of GLO 1 (27%) and GLO 2 (11%) causing weakening of the innate detoxification system. This is followed by an increase of RAGE (95%), AGEs or methylglyoxal adducts. We also observed hypoxia via estimation of oxygen consumption rate and surplus reactive oxygen species (ROS) (24%). To investigate the off‐target effect of MGO we checked its effect on glucose transport, and its associated proteins. Glucose uptake was found to increase (15%) significantly with overexpression of GLUT 1 (35%). We also found a significant increase of glycolytic enzymes such as hexokinase II, phosphofructokinase 1, and lactate dehydrogenase along with lactate production. Observation of surplus ROS and enhanced glycolysis led us to check the expression of HIF 1α which is their downstream signaling pathway. Interestingly HIF 1α was found to increase significantly (35%). It is known that enhanced glycolysis and oxidative stress are catalysts for the overexpression of HIF 1α which in turn creates an ambience for the promotion of cancer. Aminoguanidine was able to prevent the adverse effect of MGO partially. This is the first study to show the potential of MGO for the promotion of cancer in the non‐tumorigenic HepG2 cells via the Warburg effect and glycation.

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“…AGEs-derived changes in the proteome perturb signaling pathways in tissue physiology (MAP/ERK, JAK-STAT and PI3K-AKT pathways) that lead to the nuclear translocation of transcription factors involved in multiple cellular functions, including inflammation, apoptosis, ER stress, autophagy, oxidative stress, mitochondrial function, etc. (reviewed in [2,14]). Glycated proteins may also overtax or limit the function of the proteolytic capacities.…”

Section: Introduction: Glycative Stress and Unhealthy Agingmentioning

confidence: 99%

The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy

Aragonès

Rowan

Francisco

et al. 2021

Cells

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The glyoxalase system is critical for the detoxification of advanced glycation end-products (AGEs). AGEs are toxic compounds resulting from the non-enzymatic modification of biomolecules by sugars or their metabolites through a process called glycation. AGEs have adverse effects on many tissues, playing a pathogenic role in the progression of molecular and cellular aging. Due to the age-related decline in different anti-AGE mechanisms, including detoxifying mechanisms and proteolytic capacities, glycated biomolecules are accumulated during normal aging in our body in a tissue-dependent manner. Viewed in this way, anti-AGE detoxifying systems are proposed as therapeutic targets to fight pathological dysfunction associated with AGE accumulation and cytotoxicity. Here, we summarize the current state of knowledge related to the protective mechanisms against glycative stress, with a special emphasis on the glyoxalase system as the primary mechanism for detoxifying the reactive intermediates of glycation. This review focuses on glyoxalase 1 (GLO1), the first enzyme of the glyoxalase system, and the rate-limiting enzyme of this catalytic process. Although GLO1 is ubiquitously expressed, protein levels and activities are regulated in a tissue-dependent manner. We provide a comparative analysis of GLO1 protein in different tissues. Our findings indicate a role for the glyoxalase system in homeostasis in the eye retina, a highly oxygenated tissue with rapid protein turnover. We also describe modulation of the glyoxalase system as a therapeutic target to delay the development of age-related diseases and summarize the literature that describes the current knowledge about nutritional compounds with properties to modulate the glyoxalase system.

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Advanced glycation end products and their adverse effects: The role of autophagy

Cited by 19 publications

References 192 publications

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

Interplay Among the Oral Microbiome, Oral Cavity Conditions, the Host Immune Response, Diabetes Mellitus, and Its Associated-Risk Factors—An Overview

Methylglyoxal induces ambience for cancer promotion in HepG2 cells via Warburg effect and promotes glycation

The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy

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