Hyperglycemia-induced endoplasmic reticulum stress in endothelial cells

Sheikh-Ali, Mae; Sultan, Senan; Alamir, Abdul-Razzak; Haas, Michael J.; Mooradian, Arshag D.

doi:10.1016/j.nut.2009.08.019

Cited by 62 publications

(45 citation statements)

References 15 publications

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“…An additional emerging function of the ER is the regulation of apoptosis in the cell (8). A number of stimuli, including ischemia, hypoxia, hyperglycemia, gene mutation and elevated protein synthesis, are collectively referred to as ER stress and all potentially cause ER dysfunction (9,10). ER stress has been reported to be critical to the pathogenesis of a number of acute and chronic kidney diseases, including renal ischemia, acute kidney injury and diabetic kidney disease (11).…”

Section: Introductionmentioning

confidence: 99%

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

Zhao

et al. 2012

Molecular Medicine Reports

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Abstract. Diabetes mellitus is known to cause kidney impairment; however, the mechanism remains elusive. The aim of this study was to investigate the role of C/EBP homologous protein (CHOP), an important protein in endoplasmic reticulum stress-mediated mesangial cell apoptosis in hyperglycemia. Mesangial cells were cultured in normal (control group) and high glucose medium (high glucose group). TUNEL staining was performed to assess apoptotic cells in the groups. The expression of CHOP and caspase-3 was also assayed by immunohistochemistry and western blot analysis. Following 24 h culture in high glucose medium, TUNEL-positive cells were observed to be significantly increased (P<0.01). The expression of CHOP and caspase-3 in mesangial cells was also found to be significantly enhanced under high glucose conditions compared with the normal group (P<0.01). The results indicate that CHOP mediates apoptosis in mesangial cells under hyperglycemia and may play a role in the development of diabetic nephropathy.

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Section: Introductionmentioning

confidence: 99%

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

Zhao

et al. 2012

Molecular Medicine Reports

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“…20 Hyperglycemia, but not oxidative stress, also directly induces ER stress in human umbilical chord vascular endothelial cells. 33 Increased ER stress is present in the retinas of diabetic Akita mice 34 and ER stress activates vascular endothelial growth factor levels in cultured human retinal pigment epithelial cells 35 and human vascular endothelial cells. 34,36 Under nondiabetic conditions, ER stress in rat retinas has been also linked to neuronal abnormalities resulting from ischemia-reperfusion injury 37 and to retinal ganglion cell death in chronic rat glaucoma models.…”

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confidence: 99%

Response of Rat Retinal Capillary Pericytes and Endothelial Cells to Glucose

Makita

Hosoya

Zhang

et al. 2011

Journal of Ocular Pharmacology and Therapeutics

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Aim: The purpose of this study was to investigate the effects of hyperglycemia, its fluctuations, and glucose starvation on the expression of glucose-regulated protein 78/binding immunoglobulin protein (GRP78/BiP), one of the most commonly used markers of endoplasmic reticulum stress, in rat capillary pericytes and endothelial cells cultured separately and together. Methods: Conditionally immortalized rat retinal pericyte and endothelial cell lines were cultured in dishes coated with collagen type I in Dulbecco's modified Eagle's medium containing 5.5 mM glucose. For cocultures, pericytes and endothelial cells were seeded together on rat tail collagen type I-coated cell culture plates. After 24 h of initial culture, the medium was replaced with serum-free medium containing 0-100 mM glucose for periods of up to 72 h. GRP78/BiP, caspase-3, and nuclear factor-kB expression were investigated using western blots. Results: No significant increase in GRP78/BiP expression was observed when pericytes, endothelial cells, or cocultures were exposed to either 25, 50, or 100 mM glucose for 48 h compared with the control level of 5.5 mM glucose. Similarly, no change in expression of GRP78/BiP was observed when media glucose levels were reduced from either 5.5 or 25 to 1 mM. GRP78/BiP expression significantly increased when cells were cultured for 24 h in glucose-deprived medium. This was accompanied by a time-dependent increase in the expression of caspase-3 and nuclear factor-kB. Conclusion: In diabetic retinopathy, hyperglycemia has been reported to induce apoptosis in retinal capillary vascular cells, but these studies suggest that the apoptosis is not linked to the expression of GRP78/BiP, one of the most commonly used markers of endoplasmic reticulum stress. However, GRP78/BiP-linked apoptosis may play a role in vascular changes associated with retinal ischemia/reperfusion.

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“…Indeed, oxidative stress is prevalent under the condition (20). Hyperglycemia, an inducer of ER stress in vascular endothelial cells (40), seemed unlikely to be involved in uremic serum-induced ER stress, since the circulating level of glucose in rats with RRM was normal. Given CKD may be regarded as a coronary heart disease risk equivalent (41), it is essential to identify the biological substances in the serum responsible for vascular endothelial dysfunctions and dissect their related signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Vascular insulin resistance related to endoplasmic reticulum stress in aortas from a rat model of chronic kidney disease

Zhou

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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Here we tested the hypothesis that vascular insulin signaling was impaired and related with endoplasmic reticulum (ER) stress in aortas from the reduced renal mass (RRM) model of CKD. The activity of insulin signaling and markers of ER were determined in aortas from rats with RRM and cultured human umbilical vein endothelial cells. Tyrosine phosphorylation of insulin receptor-␤ and insulin receptor substrate (IRS)-1 and phosphorylation of protein kinase B and endothelial nitric oxide synthase were all decreased in aorta from RRM rats, whereas serine phosphorylation of IRS-1, a marker of insulin resistance, was increased. In addition, nitric oxide generation and insulin-mediated vasorelaxation were decreased in aortas from RRM rats. Insulin signaling in cultured vascular endothelial cells was impaired by induction of ER stress and was restored in aortas of RRM rats by inhibition of ER stress. Taken together, rats with RRM had vascular insulin resistance that was linked to ER stress. This identified vascular insulin resistance and ER stress as a potential therapeutic target for cardiovascular complications in patients with CKD.

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Hyperglycemia-induced endoplasmic reticulum stress in endothelial cells

Cited by 62 publications

References 15 publications

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

C/EBP homologous protein induces mesangial cell apoptosis under hyperglycemia

Response of Rat Retinal Capillary Pericytes and Endothelial Cells to Glucose

Vascular insulin resistance related to endoplasmic reticulum stress in aortas from a rat model of chronic kidney disease

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