Glycoxidative stress–induced mitophagy modulates mitochondrial fates

Lo, Mei-Chen; Lu, Chin I.; Chen, Ming Hong; Chen, Chun-Da; Lee, Horng Mo; Kao, Shu Huei

doi:10.1111/j.1749-6632.2010.05630.x

Cited by 26 publications

(20 citation statements)

References 38 publications

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“…We speculate that a non-enzymatic reaction that produces methylglyoxal from glyceraldehyde 3-phosphate, another minor pathway of glucose metabolism, may be involved. Methylglyoxal generates AGEs that are well-known sources of ROS under a chronic hyperglycaemic state (Dhar et al, 2008; Lo et al, 2010). The increased production of methylglyoxal and resultant increases in ROS production by AGEs in a hyperglycaemic state have been reported in the vascular system (Dhar et al, 2008; Lo et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Methylglyoxal generates AGEs that are well-known sources of ROS under a chronic hyperglycaemic state (Dhar et al, 2008; Lo et al, 2010). The increased production of methylglyoxal and resultant increases in ROS production by AGEs in a hyperglycaemic state have been reported in the vascular system (Dhar et al, 2008; Lo et al, 2010). If the adverse effects of high - glucose environments overcome the astroglial intrinsic protective mechanism in the long run, they may result in brain damage.…”

Section: Discussionmentioning

confidence: 99%

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Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

2012

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ROS (reactive oxygen species) play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain parenchymal cells remain unclear. The PPP (pentose phosphate pathway) and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of 14CO2 production from [1-14C]glucose and [6-14C]glucose. ROS production, mainly H2O2, and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum) stress (presumably through increased hexosamine biosynthetic pathway flux). Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase) by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein) expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

2012

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“…These results suggest that excessive autophagy may cause defects in ␤-cell functions and cell death. Both excess and deficit in autophagy can promote cell injury and have been linked to several diseases, including neurodegeneration and diabetes (22,36). Two research groups used autophagy-deficient, ␤-cell-specific Atg7-knockout mice to show increased apoptosis and decreased cell proliferation resulting in decreased ␤-cell mass (15,16) and to show the degeneration of ␤-cells and impaired glucose tolerance with reduced insulin secretion as well as poor stress response to high-fat diets (10, 11).…”

Section: Discussionmentioning

confidence: 99%

N^ε-(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from β-cells

Chen²,

Lee

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

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Lo MC, Chen MH, Lee WS, Lu CI, Chang CR, Kao SH, Lee HM. N ε -(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from ␤-cells. Am J Physiol Endocrinol Metab 309: E829 -E839, 2015. First published September 22, 2015; doi:10.1152/ajpendo.00151.2015 ε -(carboxymethyl) lysine-conjugated bovine serum albumin (CML-BSA) is a major component of advanced glycation end products (AGEs). We hypothesised that AGEs reduce insulin secretion from pancreatic ␤-cells by damaging mitochondrial functions and inducing mitophagy. Mitochondrial morphology and the occurrence of autophagy were examined in pancreatic islets of diabetic db/db mice and in the cultured CML-BSA-treated insulinoma cell line RIN-m5F. In addition, the effects of ␣-lipoic acid (ALA) on mitochondria in AGEdamaged tissues were evaluated. The diabetic db/db mouse exhibited an increase in the number of autophagosomes in damaged mitochondria and receptor for AGEs (RAGE). Treatment of db/db mice with ALA for 12 wk increased the number of mitochondria with wellorganized cristae and fewer autophagosomes. Treatment of RIN-m5F cells with CML-BSA increased the level of RAGE protein and autophagosome formation, caused mitochondrial dysfunction, and decreased insulin secretion. CML-BSA also reduced mitochondrial membrane potential and ATP production, increased ROS and lipid peroxide production, and caused mitochondrial DNA deletions. Elevated fission protein dynamin-related protein 1 (Drp1) level and mitochondrial fragmentation demonstrated the unbalance of mitochondrial fusion and fission in CML-BSA-treated cells. Additionally, increased levels of Parkin and PTEN-induced putative kinase 1 protein suggest that fragmented mitochondria were associated with increased mitophagic activity, and ALA attenuated the CML-BSAinduced mitophage formation. Our study demonstrated that CML-BSA induced mitochondrial dysfunction and mitophagy in pancreatic ␤-cells. The findings from this study suggest that increased concentration of AGEs may damage ␤-cells and reduce insulin secretion. advanced glycated end products; mitochondrial dynamics; mitophagy; diabetes DIABETES MELLITUS IS CHARACTERIZED BY HYPERGLYCEMIA and long-term irreversible change of vascular and connective tissue. Advanced glycated end products (AGEs) have been directly implicated in the development of chronic complications of diabetes such as nephropathy, arteriosclerosis, retinopathy, neuropathy, and cataracts (30). AGEs can be formed via either the nonenzymatic "Maillard reaction" or increased polyol pathway flux (14). In particular, the reactive carbonyl group of methylglyoxal reacts with the amino group of lysine to produce protein conjugates with 3-deoxyglucosone-imidazolone, pyrraline, pentosidine, and N ε -(carboxymethyl) lysine (14). AGEs may impair insulin secretion and lead to the development of diabetes (7). A previous report showed that serum levels of N ε -(carboxymethyl) lysine-conjugated AGEs, a major constituent of AGEs, were elevated up to 42-44 U/ml in 7-mo-ol...

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“…Accumulation of advanced glycation end products (AGEs) due to chronic hyperglycaemia induces glycoxidative stress in DM, leading to massive mitochondrial dysfunction. Mitophagy is important in protecting cells from mitochondrial toxicity in DM condition [12]. Indeed, mitophagy induction in diabetic platelets protects it against oxidative stress-induced mitochondrial damage and apoptosis, thereby reducing thrombotic injuries in DM [50].…”

Section: Mitochondrial Quality Control: Different Types Of Mitophagymentioning

confidence: 99%

“…Defects in mitophagy result in accumulation of dysfunctional mitochondria seen in aging and age-related disorders [9–11]. Conversely, upregulation of mitophagy successfully ameliorates mitochondrial dysfunction and cell toxicity in diseases like diabetes mellitus (DM) and Parkinson's disease [12, 13]. Most significantly, enhanced mitophagy activity extends lifespan and healthspan in Caenorhabditis elegans ( C. elegans ) and mouse models [14–17].…”

Section: Introductionmentioning

confidence: 99%

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol‐Mediated Mitophagy

Tan

Wong

2017

Oxidative Medicine and Cellular Longevity

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Mitochondria are important bioenergetic and signalling hubs critical for myriad cellular functions and homeostasis. Dysfunction in mitochondria is a central theme in aging and diseases. Mitophagy, a process whereby damaged mitochondria are selectively removed by autophagy, plays a key homeostatic role in mitochondrial quality control. Upregulation of mitophagy has shown to mitigate superfluous mitochondrial accumulation and toxicity to safeguard mitochondrial fitness. Hence, mitophagy is a viable target to promote longevity and prevent age-related pathologies. Current challenge in modulating mitophagy for cellular protection involves identification of physiological ways to activate the pathway. Till date, mitochondrial stress and toxins remain the most potent inducers of mitophagy. Polyphenols have recently been demonstrated to protect mitochondrial health by facilitating mitophagy, thus suggesting the exciting prospect of augmenting mitophagy through dietary intake. In this review, we will first discuss the different surveillance mechanisms responsible for the removal of damaged mitochondrial components, followed by highlighting the transcriptional regulatory mechanisms of mitophagy. Finally, we will review the functional connection between polyphenols and mitophagy and provide insight into the underlying mechanisms that potentially govern polyphenol-induced mitophagy.

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Glycoxidative stress–induced mitophagy modulates mitochondrial fates

Cited by 26 publications

References 38 publications

Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

N^ε-(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from β-cells

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol‐Mediated Mitophagy

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Glycoxidative stress–induced mitophagy modulates mitochondrial fates

Cited by 26 publications

References 38 publications

Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

Nε-(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from β-cells

Mitophagy Transcriptome: Mechanistic Insights into Polyphenol‐Mediated Mitophagy

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N^ε-(carboxymethyl) lysine-induced mitochondrial fission and mitophagy cause decreased insulin secretion from β-cells