Protective Effect of Fenofibrate on Oxidative Stress-Induced Apoptosis in Retinal–Choroidal Vascular Endothelial Cells: Implication for Diabetic Retinopathy Treatment

Diabetic retinopathy (DR) is an important microvascular complication of diabetes and one of the leading causes of blindness in developed countries. Two large clinical studies showed that fenofibrate, a peroxisome proliferator-activated receptor type α (PPAR-α) agonist, reduces DR progression. We evaluated the protective effects of fenofibrate on retinal/choroidal vascular endothelial cells under oxidative stress and investigated the underlying mechanisms using RF/6A cells as the model system and paraquat (PQ) to induce oxidative stress. Pretreatment with fenofibrate suppressed reactive oxygen species (ROS) production, decreased cellular apoptosis, diminished the changes in the mitochondrial membrane potential, increased the mRNA levels of peroxiredoxin (Prx), thioredoxins (Trxs), B-cell lymphoma 2 (Bcl-2), and Bcl-xl, and reduced the level of B-cell lymphoma 2-associated X protein (Bax) in PQ-stimulated RF/6A cells. Western blot analysis revealed that fenofibrate repressed apoptosis through cytosolic and mitochondrial apoptosis signal-regulated kinase-1 (Ask)-Trx-related signaling pathways, including c-Jun amino-terminal kinase (JNK) phosphorylation, cytochrome c release, caspase 3 activation, and poly (ADP-ribose) polymerase-1 (PARP-1) cleavage. These protective effects of fenofibrate on RF/6A cells may be attributable to its anti-oxidative ability. Our research suggests that fenofibrate could serve as an effective adjunct therapy for ocular oxidative stress-related disorders, such as DR.

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Sirt1 Inhibits Oxidative Stress in Vascular Endothelial Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7543973 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 51

Author(s):

Weijin Zhang ◽

Qiaobing Huang ◽

Zhenhua Zeng ◽

Jie Wu ◽

Yaoyuan Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Vascular Endothelial Cells ◽

Protective Role ◽

Vascular Endothelial ◽

Protective Effects ◽

Beneficial Effects ◽

Key Factor ◽

Antioxidative Stress

The vascular endothelium is a layer of cells lining the inner surface of vessels, serving as a barrier that mediates microenvironment homeostasis. Deterioration of either the structure or function of endothelial cells (ECs) results in a variety of cardiovascular diseases. Previous studies have shown that reactive oxygen species (ROS) is a key factor that contributes to the impairment of ECs and the subsequent endothelial dysfunction. The longevity regulator Sirt1 is a NAD+-dependent deacetylase that has a potential antioxidative stress activity in vascular ECs. The mechanisms underlying the protective effects involve Sirt1/FOXOs, Sirt1/NF-κB, Sirt1/NOX, Sirt1/SOD, and Sirt1/eNOs pathways. In this review, we summarize the most recent reports in this field to recapitulate the potent mechanisms involving the protective role of Sirt1 in oxidative stress and to highlight the beneficial effects of Sirt1 on cardiovascular functions.

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Curcumin suppresses oxidative stress via regulation of ROS/NF-κB signaling pathway to protect retinal vascular endothelial cell in diabetic retinopathy

10.21203/rs.3.rs-27239/v1 ◽

2020 ◽

Author(s):

Jiang Huang ◽

Quanyong Yi ◽

Yao Chen ◽

Yi Li ◽

Guoxu Xu ◽

...

Keyword(s):

Oxidative Stress ◽

Flow Cytometry ◽

Endothelial Cells ◽

Diabetic Retinopathy ◽

High Glucose ◽

Glucose Concentration ◽

Vascular Endothelial Cells ◽

Control Group ◽

Vascular Endothelial ◽

High Glucose Concentration

Abstract Background: Diabetic retinopathy (DR) is one of the most serious complications of diabetes mellitus and a leading blindness disease in the world. The retinal vascular endothelial cells can be damaged by oxidative stress even in the early stage of diabetic retinopathy. NF-κB is a key transcription factor in cell apoptosis and oxidative stress. Curcumin can relieve oxidative stress induced by high glucose. This study aimed to investigate the effect of curcumin on the rat retinal vascular endothelial cells (RRVECs) in DR and to deduce the possible molecular mechanism. Methods: The cultured RRVECs were identified by both of vWF and CD31 expression.The RRVECs were divided into four groups: the normal control group, the osmolarity control group, the high glucose group and the curcumin treatment group (High glucose +Curcumin). We observed the different morphological changes in the groups by transmission electron microscopy. Oxidative stress was detected by flow cytometry. The Activation of ROS/NF-κB signal pathway was detected by electrophoretic Mobility Shift Assay (EMSA), immunohistochemistry and western-blot; the apoptosis of RRVECs was tested by flow cytometry. Results: We found that curcumin reduced the reactive oxygen species (ROS) and relieved the apoptosis in RRVECs exposed to the high glucose by flow cytometry. We detected that the increased activity of NF-κB and phosphorylated NF-κB in RRVECs induced by high glucose concentration was significantly suppressed by curcumin. Furthermore, based on the assay quantifying the level of apoptosis-related proteins, including bcl-2 and bax, we illustrated that curcumin could decrease the apoptosis of RRVECs induced by high glucose concentration. Conclusion: We concluded that ROS/NF-κB signaling pathway played an important role in the progress of DR and curcumin could suppress the oxidative stress via regulation of NF-κB signal to protect the RRVECs in DR.

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Alisol A 24-acetate protects oxygen–glucose deprivation-induced brain microvascular endothelial cells against apoptosis through miR-92a-3p inhibition by targeting the B-cell lymphoma-2 gene

Pharmaceutical Biology ◽

10.1080/13880209.2021.1912117 ◽

2021 ◽

Vol 59 (1) ◽

pp. 513-524

Author(s):

Yangjie Zhou ◽

Wei Wei ◽

Julian Shen ◽

Lu Lu ◽

Taotao Lu ◽

...

Keyword(s):

Endothelial Cells ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Glucose Deprivation ◽

Microvascular Endothelial Cells ◽

Oxygen Glucose Deprivation ◽

Brain Microvascular Endothelial Cells ◽

Microvascular Endothelial

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Z-Ligustilide protects vascular endothelial cells from oxidative stress and rescues high fat diet-induced atherosclerosis by activating multiple NRF2 downstream genes

Atherosclerosis ◽

10.1016/j.atherosclerosis.2019.02.010 ◽

2019 ◽

Vol 284 ◽

pp. 110-120 ◽

Cited By ~ 13

Author(s):

Yao Zhu ◽

Yajie Zhang ◽

Xia Huang ◽

Yong Xie ◽

Yuan Qu ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

High Fat Diet ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

High Fat

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The protective effects of HGF against apoptosis in vascular endothelial cells caused by peripheral vascular injury

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmy048 ◽

2018 ◽

Vol 50 (7) ◽

pp. 701-708 ◽

Cited By ~ 2

Author(s):

Wu Zhong ◽

Yu Zhao ◽

Ye Tian ◽

Muhu Chen ◽

Xue Lai

Keyword(s):

Endothelial Cells ◽

Vascular Injury ◽

Vascular Endothelial Cells ◽

Vascular Endothelial ◽

Protective Effects ◽

Peripheral Vascular

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Glutamate induces oxidative stress and apoptosis in cerebral vascular endothelial cells: contributions of HO-1 and HO-2 to cytoprotection

AJP Cell Physiology ◽

10.1152/ajpcell.00386.2005 ◽

2006 ◽

Vol 290 (5) ◽

pp. C1399-C1410 ◽

Cited By ~ 112

Author(s):

Helena Parfenova ◽

Shyamali Basuroy ◽

Sujoy Bhattacharya ◽

Dilyara Tcheranova ◽

Yan Qu ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Endothelial Cells ◽

Vascular Endothelium ◽

Vascular Endothelial Cells ◽

Glutamate Toxicity ◽

Vascular Endothelial ◽

Oxygen Species ◽

Apoptotic Effects ◽

Cerebral Vascular

In cerebral circulation, epileptic seizures associated with excessive release of the excitatory neurotransmitter glutamate cause endothelial injury. Heme oxygenase (HO), which metabolizes heme to a vasodilator, carbon monoxide (CO), and antioxidants, biliverdin/bilirubin, is highly expressed in cerebral microvessels as a constitutive isoform, HO-2, whereas the inducible form, HO-1, is not detectable. Using cerebral vascular endothelial cells from newborn pigs and HO-2-knockout mice, we addressed the hypotheses that 1) glutamate induces oxidative stress-related endothelial death by apoptosis, and 2) HO-1 and HO-2 are protective against glutamate cytotoxicity. In cerebral endothelial cells, glutamate (0.1–2.0 mM) increased formation of reactive oxygen species, including superoxide radicals, and induced major keystone events of apoptosis, such as NF-κB nuclear translocation, caspase-3 activation, DNA fragmentation, and cell detachment. Glutamate-induced apoptosis was greatly exacerbated in HO-2 gene-deleted murine cerebrovascular endothelial cells and in porcine cells with pharmacologically inhibited HO-2 activity. Glutamate toxicity was prevented by superoxide dismutase, suggesting apoptotic changes are oxidative stress related. When HO-1 was pharmacologically upregulated by cobalt protoporphyrin, apoptotic effects of glutamate in cerebral endothelial cells were completely prevented. Glutamate-induced reactive oxygen species production and apoptosis were blocked by a CO-releasing compound, CORM-A1 (50 μM), and by bilirubin (1 μM), consistent with the antioxidant and cytoprotective roles of the end products of HO activity. We conclude that both HO-1 and HO-2 have anti-apoptotic effects against oxidative stress-related glutamate toxicity in cerebral vascular endothelium. Although HO-1, when induced, provides powerful protection, HO-2 is an essential endogenous anti-apoptotic factor against glutamate toxicity in the cerebral vascular endothelium.

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