TRIM46 contributes to high glucose-induced ferroptosis and cell growth inhibition in human retinal capillary endothelial cells by facilitating GPX4 ubiquitination

Zhang, Jingfa; Qiu, Qinghua; Wang, Haiyan; Chen, Chong; Luo, Da

doi:10.1016/j.yexcr.2021.112800

Cited by 94 publications

(84 citation statements)

References 45 publications

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“…As a new mechanism of cell death, the discovery of ferroptosis and the mechanisms involved in its regulation may help to develop novel treatments for several diseases. Recent studies have documented significant effects of ferroptosis on the development and progression of T1DM ( 59 ); T2DM ( 60 , 61 ); gestational diabetes mellitus ( 60 – 62 ); and diabetes complications such as DKD ( 27 ), DCM ( 29 ), DR ( 63 , 64 ), diabetes-induced endothelial dysfunction ( 32 ), cognitive dysfunction ( 31 ), wound healing ( 65 ), diabetic atherosclerosis ( 66 ), and DOP ( 67 ). The molecular mechanisms of ferroptosis in diabetic complications involve multiple proteins, including acyl-CoA synthetase long chain family member 4 (ACSL4), high-mobility group box-1 (HMGB1), hypoxia-inducible factor-1α (HIF-1α), heme oxygenase-1 (HO-1), tripartite motif containing 46 (TRIM46), circ-PSEN1, NCOA4 ( 68 ), and Nox2, and negative genes, Gpx4 , Nrf2 , xCT , adenosine monophosphate-activated protein kinase, heat shock factor 1 ( HSF1 ), and nutrient-deprivation autophagy factor-1 ( NAF-1 ) ( 69 ) ( Figure 2 ).…”

Section: Effects and The Molecular Mechanisms Of Ferroptosis On Diabe...mentioning

confidence: 99%

“…HG inhibits human RCEC growth and induces ferroptosis, which can be reversed by Fer-1. TRIM46 mediated Gpx4 ubiquitination pathway is involved in HG-induced ferroptosis in human RCECs ( 63 ). In addition to microvascular changes, retinal neurodegeneration or loss of the retinal pigment epithelium (RPE) also contribute to diabetic retinal damage early in DR, and HG has detrimental effects on RPE cells by producing ROS and decreasing the Gpxs expression ( 109 ).…”

Section: Effects and The Molecular Mechanisms Of Ferroptosis On Diabe...mentioning

confidence: 99%

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Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications

Yang

2022

Front. Endocrinol.

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The global diabetes epidemic and its complications are increasing, thereby posing a major threat to public health. A comprehensive understanding of diabetes mellitus (DM) and its complications is necessary for the development of effective treatments. Ferroptosis is a newly identified form of programmed cell death caused by the production of reactive oxygen species and an imbalance in iron homeostasis. Increasing evidence suggests that ferroptosis plays a pivotal role in the pathogenesis of diabetes and diabetes-related complications. In this review, we summarize the potential impact and regulatory mechanisms of ferroptosis on diabetes and its complications, as well as inhibitors of ferroptosis in diabetes and diabetic complications. Therefore, understanding the regulatory mechanisms of ferroptosis and developing drugs or agents that target ferroptosis may provide new treatment strategies for patients with diabetes.

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Section: Effects and The Molecular Mechanisms Of Ferroptosis On Diabe...mentioning

confidence: 99%

Section: Effects and The Molecular Mechanisms Of Ferroptosis On Diabe...mentioning

confidence: 99%

Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications

Yang

2022

Front. Endocrinol.

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“…This change is closely related to the occurrence of ferroptosis. Recent studies have shown that high glucose treatment induces ferroptosis in human retinal capillary endothelial cells (HRCECs) by up-regulating TRIM46, inducing ubiquitination, and accelerating GPX4 clearance [ 102 ].…”

Section: Ferroptosis and Ferritinophagy Participate In The Pathogenes...mentioning

confidence: 99%

Ferroptosis and ferritinophagy in diabetes complications

Xia

et al. 2022

Molecular Metabolism

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“…TRIM46 may be a potential biomarker of carcinogenesis and regulates the proliferation of cancer cells via mediated VEGF ( 67 ). Through in vitro experiments, a recent study found that high glucose treatment time-dependently induced ferroptosis in HRCECs and induced TRIM46 expression ( 68 ). Overexpression of TRIM46 mediated by lentiviral strongly weakened cell resistance against ferroptosis in HRCECs in response to high glucose, whereas RNAi-mediated knockdown of TRIM46 had the opposite effect.…”

Section: Research Progress Into Ferroptosis In Ophthalmologymentioning

confidence: 99%

Molecular Mechanisms of Iron Mediated Programmed Cell Death and Its Roles in Eye Diseases

et al. 2022

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Ferroptosis, a newly identified, iron-dependent type of programmed cell death, is active in several diseases, such as heart disease, brain damage, and cancer. Its main characteristics commonly involve excess iron accumulation, elevated lipid peroxides and reactive oxygen species, and reduced levels of glutathione and glutathione peroxidase 4 levels. The effects of ferroptosis in eye diseases cannot be underestimated, with ferroptosis becoming a research target in ocular disorders and emerging evidence from a series of in vivo and in vitro researches into ferroptosis revealing its role in eye conditions. However, no report provides comprehensive information on the pathophysiology of ferroptosis in eye diseases and its possible treatments. In the current review, we present an up-to-date overview of ferroptosis biology and its involvement in the pathological processes of ocular diseases. Furthermore, we pose several outstanding questions and areas for future research in this topic. We deem ferroptosis-associated cell death a pivotal new field of scientific study in ocular diseases and consider it a new therapeutic target in the treatment of some eye disorders.

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TRIM46 contributes to high glucose-induced ferroptosis and cell growth inhibition in human retinal capillary endothelial cells by facilitating GPX4 ubiquitination

Cited by 94 publications

References 45 publications

Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications

Ferroptosis as a Novel Therapeutic Target for Diabetes and Its Complications

Ferroptosis and ferritinophagy in diabetes complications

Molecular Mechanisms of Iron Mediated Programmed Cell Death and Its Roles in Eye Diseases

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