Beta-adrenergic receptor stimulation modulates iNOS protein levels through p38 and ERK1/2 signaling in human retinal endothelial cells

Steinle, Jena J.; Chin, Vannak C.; Williams, Kimberly P.; Panjala, Surekha Rani

doi:10.1016/j.exer.2008.04.008

Cited by 19 publications

(17 citation statements)

References 19 publications

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“…We have previously shown that beta adrenergic signaling can reduce inflammatory markers in retinal Müller cells [27] and endothelial cells [8,15]. b-adrenergic receptor stimulation can reduce the cleavage of caspase 3 through Fas signaling of retinal endothelial cells cultured in high glucose [4].…”

Section: Igf-1 Receptors and Insulin Receptors On Retinal Endothelialmentioning

confidence: 98%

“…Once cells reached *80% confluence, cells were switched to medium (containing 25 mM glucose) with 0% FBS and antibiotics for 18-24 h to eliminate any residual effects of FBS. Following starvation, four dishes were treated with 10 lM xamoterol, a selective beta -1-adrenergic receptor agonist, at each time point of 15, 30, and 45 min [8]. In addition, four dishes were not treated and served as non-treated (NT) controls.…”

Section: Culture Of Primary Human Retinal Microvascular Endothelial Cmentioning

confidence: 99%

“…In this study, we specifically targeted b-1-adrenergic receptor, using xamoterol, on human retinal endothelial cells cultured in high glucose to mimic diabetic conditions [7]. Stimulation of b-1-adrenergic receptors with 10 lM xamoterol can prevent/reduce many changes common to diabetic retinopathy, such as apoptosis and inflammatory marker activation [4,8]. b-adrenergic receptors may modulate insulin receptor/IGF-1 receptor signaling in the retina and play a significant role in retinal pathology.…”

Section: Introductionmentioning

confidence: 99%

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Insulin and β-adrenergic Receptors Inhibit Retinal Endothelial Cell Apoptosis Through Independent Pathways

Panjala

Steinle

2010

Neurochem Res

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Diabetic retinopathy results from altered insulin receptor signaling. Based on previous studies demonstrating an interaction between β-adrenergic receptors and insulin signaling in hyperglycemic conditions, we hypothesized that β-adrenergic receptor stimulation and insulin stimulation would act synergistically to inhibit one of the hallmarks of diabetic retinopathy, namely retinal endothelial cell apoptosis. To test this hypothesis, human retinal endothelial cells were grown in high glucose (25 mM) medium and treated with a β-1-adrenergic receptor agonist (xamoterol, 10 μM) alone, insulin alone (10 nM) or xamoterol + insulin. We then assessed changes in the levels of insulin receptor, insulin-like growth factor (IGF-1) receptor, and Akt phosphorylation, as well as cleaved caspase 3. Xamoterol alone significantly decreased insulin receptor, IGF-1 receptor and Akt phosphorylation, whereas insulin alone increased insulin receptor, IGF-1 receptor, and Akt phosphorylation. Xamoterol significantly decreased apoptosis of retinal endothelial cells. This data suggests that both β-adrenergic receptors and insulin can inhibit retinal endothelial cell apoptosis in hyperglycemic conditions, but inhibition occurs through independent pathways. These findings have implications for treatments of diabetic retinopathy.

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Section: Igf-1 Receptors and Insulin Receptors On Retinal Endothelialmentioning

confidence: 98%

Section: Culture Of Primary Human Retinal Microvascular Endothelial Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin and β-adrenergic Receptors Inhibit Retinal Endothelial Cell Apoptosis Through Independent Pathways

Panjala

Steinle

2010

Neurochem Res

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“…73 In addition, daily administration of the b-adrenergic receptor agonist, isoproterenol, significantly reduced the diabetes-induced loss of electroretinographic amplitudes, inhibited apoptosis of retinal neural cells, and decreased the numbers of degenerate capillaries. 71,74,75 …”

Section: G-proteinecoupled Receptor Agonists and Antagonistsmentioning

confidence: 99%

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Roy

Kern

Song

et al. 2017

The American Journal of Pathology

171

147

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Increasing evidence points to inflammation as one of the key players in diabetes-mediating adverse effects to the neuronal and vascular components of the retina. Sustained inflammation induces biochemical and molecular changes, ultimately contributing to retinal complications and vision loss in diabetic retinopathy. In this review, we describe changes involving metabolic abnormalities secondary to hyperglycemia, oxidative stress, and activation of transcription factors, together with neuroglial alterations in the diabetic retina. Changes in biochemical pathways and how they promote pathophysiologic developments involving proinflammatory cytokines, chemokines, and adhesion molecules are discussed. Inflammation-mediated leukostasis, retinal ischemia, and neovascularization and their contribution to pathological and clinical stages leading to vision loss in diabetic retinopathy (DR) are highlighted. In addition, potential treatment strategies involving fibrates, connexins, neuroprotectants, photobiomodulation, and anti-inflammatory agents against the development and progression of DR lesions are reviewed. The importance of appropriate animal models for testing novel strategies against DR lesions is discussed; in particular, a novel nonhuman primate model of DR and the suitability of rodent models are weighed. The purpose of this review is to highlight our current understanding of the pathogenesis of DR and to summarize recent advances using novel approaches or targets to investigate and inhibit the retinopathy. (Am J Pathol 2017, 187: 9e19; http://dx

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“…118,123 Previous studies in our lab using primary cultures of human retinal endothelial cells with treatment of a selective ß1-adrenergic receptor agonist, in a high glucose environment showed significant increases in PKA levels through 15-45 minute treatments. 124 These results suggest that stimulation of ß1-adrenergic receptors activate the signaling of G s -adenylyl cyclase-cAMP-PKA, which is in contrast to the findings reported here on ß2-adrenergic receptors.…”

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confidence: 57%

Beta-2-Adrenergic Receptor Regulates Insulin Signaling to Reduce Cell Death in Müller Cells

Walker¹

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Beta-adrenergic receptor stimulation modulates iNOS protein levels through p38 and ERK1/2 signaling in human retinal endothelial cells

Cited by 19 publications

References 19 publications

Insulin and β-adrenergic Receptors Inhibit Retinal Endothelial Cell Apoptosis Through Independent Pathways

Insulin and β-adrenergic Receptors Inhibit Retinal Endothelial Cell Apoptosis Through Independent Pathways

Mechanistic Insights into Pathological Changes in the Diabetic Retina

Beta-2-Adrenergic Receptor Regulates Insulin Signaling to Reduce Cell Death in Müller Cells

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