Synergism between phospholipase D2 and sorbitol accumulation in diabetic cataract formation through modulation of Na,K-ATPase activity and osmotic stress

Huang, Ping; Jiang, Zhong‐Xing; Teng, Shuzhi; Wong, Yuk Chor; Frohman, Michael A.; Chung, Sookja K.; Chung, Stephen S.

doi:10.1016/j.exer.2006.05.001

Cited by 9 publications

(6 citation statements)

References 45 publications

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“…Other studies indicate that elevated oxidative stress caused by glucose metabolism through the polyol pathway, rather than osmotic stress, is the underlying cause of many diabetic complications (117). Studies using in vivo mouse models of diabetic cataract formation identified both oxidative stress (as a result of glucose metabolism) and osmotic stress as contributing to the pathology (118, 119). It has also been suggested that chronic oxidative stress associated with glucose metabolism impairs osmoregulatory pathways, thereby hindering a tissue’s ability to respond to osmotic stress (119).…”

Section: Insulin Resistance and Diabetesmentioning

confidence: 99%

The role of hyperosmotic stress in inflammation and disease

Brocker

Thompson²,

Vasiliou

2012

BioMolecular Concepts

236

212

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Hyperosmotic stress is an often overlooked process that potentially contributes to a number of human diseases. Whereas renal hyperosmolarity is a well-studied phenomenon, recent research provides evidence that many non-renal tissues routinely experience hyperosmotic stress that may contribute significantly to disease initiation and progression. Moreover, a growing body of evidence implicates hyperosmotic stress as a potent inflammatory stimulus by triggering proinflammatory cytokine release and inflammation. Under physiological conditions, the urine concentrating mechanism within the inner medullary region of the mammalian kidney exposes cells to high extracellular osmolarity. As such, renal cells have developed many adaptive strategies to compensate for increased osmolarity. Hyperosmotic stress is linked to many maladies, including acute and chronic, as well as local and systemic, inflammatory disorders. Hyperosmolarity triggers cell shrinkage, oxidative stress, protein carbonylation, mitochondrial depolarization, DNA damage, and cell cycle arrest, thus rendering cells susceptible to apoptosis. However, many adaptive mechanisms exist to counter the deleterious effects of hyperosmotic stress, including cytoskeletal rearrangement and up-regulation of antioxidant enzymes, transporters, and heat shock proteins. Osmolyte synthesis is also up-regulated and many of these compounds have been shown to reduce inflammation. The cytoprotective mechanisms and associated regulatory pathways that accompany the renal response to hyperosmolarity are found in many non-renal tissues, suggesting cells are commonly confronted with hyperosmotic conditions. Osmoadaptation allows cells to survive and function under potentially cytotoxic conditions. This review covers the pathological consequences of hyperosmotic stress in relation to disease and emphasizes the importance of considering hyperosmolarity in inflammation and disease progression.

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Section: Insulin Resistance and Diabetesmentioning

confidence: 99%

The role of hyperosmotic stress in inflammation and disease

Brocker

Thompson²,

Vasiliou

2012

BioMolecular Concepts

236

212

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“…Transgenic hyperglycemic mice overexpressing AR and phospholipase D (PLD) genes became susceptible to develop diabetic cataract in contrast to diabetic mice overexpressing PLD alone, an enzyme with key functions in the osmoregulation of the lens [16]. These findings show that impairments in the osmoregulation may render the lens susceptible to even small increases of AR-mediated osmotic stress, potentially leading to progressive cataract formation.…”

Section: Pathogenesis Of Diabetic Cataractmentioning

confidence: 99%

Diabetic Cataract—Pathogenesis, Epidemiology and Treatment

Pollreisz

Schmidt‐Erfurth

2010

Journal of Ophthalmology

318

258

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Cataract in diabetic patients is a major cause of blindness in developed and developing countries. The pathogenesis of diabetic cataract development is still not fully understood. Recent basic research studies have emphasized the role of the polyol pathway in the initiation of the disease process. Population-based studies have greatly increased our knowledge concerning the association between diabetes and cataract formation and have defined risk factors for the development of cataract. Diabetic patients also have a higher risk of complications after phacoemulsification cataract surgery compared to nondiabetics. Aldose-reductase inhibitors and antioxidants have been proven beneficial in the prevention or treatment of this sightthreatening condition in in vitro and in vivo experimental studies. This paper provides an overview of the pathogenesis of diabetic cataract, clinical studies investigating the association between diabetes and cataract development, and current treatment of cataract in diabetics.

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“…Lens culture in HG condition demonstrated the inhibitory activity of BGG as evidenced by decreased accumulation of sorbitol [31], an inducer of osmotic stress associated with diabetic cataract development [33]. BGG has low cytotoxicity and is capable of reducing ROS production and mitogen-activated protein kinase (MAPK) activation triggered by endotoxin [27].…”

Section: Introductionmentioning

confidence: 99%

Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells

Chang

Snow

LaBarbera

et al. 2015

Chemico-Biological Interactions

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Chronic hyperglycemia is an important risk factor involved in the onset and progression of diabetic retinopathy (DR). Among other effectors, aldose reductase (AR) has been linked to the pathogenesis of this degenerative disease. The purpose of this study was to investigate whether the novel AR inhibitor, beta-glucogallin (BGG), can offer protection against various hyperglycemia-induced abnormalities in human adult retinal pigment epithelia (ARPE-19) cells. AR is an enzyme that contributes to cellular stress by production of reactive oxygen species (ROS) under high glucose conditions. A marked decrease in cell viability (from 100% to 78%) following long-term exposure (4 days) of RPE cells to high glucose (HG) was largely prevented by siRNA-mediated knockdown of AR gene expression (from 79% to 97%) or inhibition using sorbinil (from 66% to 86%). In HG, BGG decreased sorbitol accumulation (44%), ROS production (27%) as well as ER stress (22%). Additionally, we demonstrated that BGG prevented loss of mitochondrial membrane potential (MMP) under HG exposure. We also showed that AR inhibitor pretreatment reduced retinal microglia-induced apoptosis in APRE-19 cells. These results suggest that BGG may be useful as a therapeutic agent against retinal degeneration in the diabetic eye by preventing RPE cell death.

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Synergism between phospholipase D2 and sorbitol accumulation in diabetic cataract formation through modulation of Na,K-ATPase activity and osmotic stress

Cited by 9 publications

References 45 publications

The role of hyperosmotic stress in inflammation and disease

The role of hyperosmotic stress in inflammation and disease

Diabetic Cataract—Pathogenesis, Epidemiology and Treatment

Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells

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