Nerve Growth Factor Blocks the Glucose-induced Down-regulation of Caveolin-1 Expression in Schwann Cells via p75 Neurotrophin Receptor Signaling

Tan, Wenbin; Rouen, Shefali; Barkus, K.; Dremina, Yelena S.; Hui, Dongwei; Christianson, Julie A.; Wright, Douglas E.; Yoon, Sung Ok; Dobrowsky, Rick T.

doi:10.1074/jbc.m212986200

Cited by 33 publications

(29 citation statements)

References 59 publications

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“…In accordance to this, Cav-1 and IR are no longer activated. Hyperglycemia could also be contributing to Cav-1 downregulation at this stage, as other authors have shown in Schwann cells [25]. Cav-1 expression pattern is similar to that observed in adipose tissue in previous studies, while Cav-2 behaves in the opposite way [26,27], suggesting that they are inversely regulated.…”

Section: Discussionsupporting

confidence: 86%

Time‐dependent regulation of muscle caveolin activation and insulin signalling in response to high‐fat diet

et al. 2009

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a b s t r a c tWe studied the effect of high-fat diet on the expression and activation of the three caveolins in rat skeletal muscle and their association with the insulin signalling cascade. Initial response was characterized by increased signalling through Cav-1 and Cav-3 phosphorylation, suggesting that both participate in an initial acute response to the calorie surplus. Afterwards, Cav-1 signalling was slightly reduced, whereas Cav-3 remained active. Late chronic phase signalling through both proteins was impaired inducing a prediabetic state. Summarizing, caveolins seem to mediate a timedependent regulation of insulin cascade in response to high-fat diet in muscle.

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Section: Discussionsupporting

confidence: 86%

Time‐dependent regulation of muscle caveolin activation and insulin signalling in response to high‐fat diet

et al. 2009

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“…In support of the view that CAV-1 plays a role in diabetes-induced changes in eNOS targeting and phosphorylation are parallel shifts in membrane CAV-1, total eNOS, and phosphorylated eNOS expressions induced by moderate hyperglycemia and improved metabolic control with intensive insulin treatment. Of interest, a similar CAV-1 regulatory pattern as in the present studies (downregulation of its expression and its reversal with insulin treatment) has recently been reported in Schwann cells, implicating this process in diabetic neuropathy as well (47).…”

Section: Enos and Cav-1 In The Diabetic Kidneysupporting

confidence: 87%

“…Similarly, eNOS phosphorylation was also normalized in diabetic rats on intensive insulin treatment. This phenomenon and the previous report in Schwann cells (47) indicate that hyperglycemia and/or low plasma insulin levels are most likely major factors in this process. Moreover, reversal of impaired eNOS phosphorylation in diabetic rats on intensive insulin treatment could be attributable not only to improved glycemic control but even more closely to higher plasma insulin doses resulting in enhanced signaling via Akt kinase (11,12).…”

Section: Enos and Cav-1 In The Diabetic Kidneysupporting

confidence: 80%

Altered Endothelial Nitric Oxide Synthase Targeting and Conformation and Caveolin-1 Expression in the Diabetic Kidney

et al. 2006

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Experimental diabetes is associated with complex changes in renal nitric oxide (NO) bioavailability. We explored the effect of diabetes on renal cortical protein expression of endothelial NO synthase (eNOS) with respect to several determinants of its enzymatic function, such as eNOS expression, membrane localization, phosphorylation, and dimerization, in moderately hyperglycemic streptozotocininduced diabetic rats compared with nondiabetic control rats and diabetic rats with intensive insulin treatment to achieve near-normal metabolic control. We studied renal cortical expression and localization of caveolin-1 (CAV-1), an endogenous modulator of eNOS function. Despite similar whole-cell eNOS expression in all groups, eNOS monomer and dimer in membrane fractions were reduced in moderately hyperglycemic diabetic rats compared with control rats; the opposite trend was apparent in the cytosol. Stimulatory phosphorylation of eNOS (Ser1177) was also reduced in moderately hyperglycemic diabetic rats. eNOS colocalized and interacted with CAV-1 in endothelial cells throughout the renal vascular tree both in control and moderately hyperglycemic diabetic rats. However, the abundance of membrane-localized CAV-1 was decreased in diabetic kidneys. Intensive insulin treatment reversed the effects of diabetes on each of these parameters. In summary, we observed diabetes-mediated alterations in eNOS and CAV-1 expression that are consistent with the view of decreased bioavailability of renal eNOS-derived NO.

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“…Evidence indicates that the effects of hyperglycaemia on Schwann cells lead to disruption of the myelin sheath, which contributes to diabetic neuropathy. In one study, hyperglycaemia induced a progressive decrease of caveolin-1 in Schwann cells in culture and in STZ-induced type 1 diabetes in mice 141 . Caveolin-1 is a structural protein found in specialized sphingolipid-cholesterol microdomains called caveolae, which are thought to be important for Schwann cell physiology because cholesterol comprises ~25% of the total lipid content of myelin 142 .…”

Section: Impact Of Schwannopathy On Neuronsmentioning

confidence: 99%

Schwann cell interactions with axons and microvessels in diabetic neuropathy

et al. 2017

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The incidence of diabetes mellitus has increased dramatically over the past two to three decades. According to the International Diabetes Federation Diabetes Atlas, 415 million people worldwide had diabetes in 2015, and this number is expected to grow by 5% annually, predominantly as a result of increasing prevalence of type 2 diabetes. Furthermore, an estimated 100 million Europeans and 80 million Americans have impaired glucose tolerance or prediabetes. Few people die from acute diabetes in countries with comprehensive health care systems, but the disease is inflicting a huge medical, social and economic burden on society owing to the need for lifelong treatment of its systemic consequences and the insidious development of multi-organ damage.Peripheral neuropathy (BOXES 1,2) is a common but often neglected complication of long-term diabetes, and the lack of treatment options reflects an incomplete understanding of the pathogenic mechanisms. Hyperglycaemia is generally accepted as the primary pathogenic insult in type 1 and type 2 diabetic neuropathy, although roles are emerging for other factors, such as impaired insulin signalling, hypertension and dyslipidaemia (particularly for type 2 diabetes), which might precede overt hyperglycaemia 1 . Many preclinical studies, and occasional clinical studies, have indicated that diabetic neuropathy -like diabetic nephropathy and retinopathy -results from microvascular disease, with a focus on axonal degeneration as a consequence of ischaemia and/or hypoxia. This mechanism, however, is likely to be only one aspect of a more complex pathogenesis.The earliest descriptions of pathology in diabetic neuropathy indicated that Schwannopathy accompanied axonal degeneration. The majority of clinical and basic research in diabetic neuropathy since then has focused on the effects on neurons. However, accumulating data from research into the development and regeneration of the PNS has identified Schwann cells as equally indispensable components that maintain neuronal structure and function, nourish axons, and promote survival and growth upon injury. The early reports from 1979 that demonstrated morphological changes in Schwann cells in human diabetic neuropathy 2 are now supported by an increased awareness of molecular alterations in Schwann cells during diabetes 3 . Schwann cells express a wide range of receptors and, when they sense insults or danger signals, they upregulate synthesis and secretion of factors that stimulate neuroprotection, regrowth and remyelination, or factors that aggravate disease phenotypes 4 . The most recent studies have demonstrated that Schwann cells regulate many aspects of axonal function, so that disruption of their metabolism by diabetes results in the accumulation of neurotoxic intermediates and compromises production of neuronal support factors, contributing to axonal degeneration, endothelial dysfunction and diabetic neuropathy. Abstract | The prevalence of diabetes worldwide is at pandemic levels, with the number of patients increasing by 5% annu...

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Nerve Growth Factor Blocks the Glucose-induced Down-regulation of Caveolin-1 Expression in Schwann Cells via p75 Neurotrophin Receptor Signaling

Cited by 33 publications

References 59 publications

Time‐dependent regulation of muscle caveolin activation and insulin signalling in response to high‐fat diet

Time‐dependent regulation of muscle caveolin activation and insulin signalling in response to high‐fat diet

Altered Endothelial Nitric Oxide Synthase Targeting and Conformation and Caveolin-1 Expression in the Diabetic Kidney

Schwann cell interactions with axons and microvessels in diabetic neuropathy

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