Endoplasmic reticulum stress and the protein degradation system in ophthalmic diseases

Song, Jing‐Yao; Wang, Xueguang; Zhang, Zi-Yuan; Che, Lin; Fan, Biao; Li, Guangyu

doi:10.7717/peerj.8638

Cited by 8 publications

(2 citation statements)

References 128 publications

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“…Endoplasmic reticulum (ER) stress is a consequence of hyperglycemia and is important in development of diabetic retinopathy, though the exact mechanism leading to damage is unclear. UBE2G2 is a key player in the ubiquitin proteasome system that is important in restoring ER homeostasis and maintaining normal ER function 44 .…”

Section: Discussionmentioning

confidence: 99%

Impact of severe hypoglycemia on the heat shock and related protein response

Atkin

Moin

Nandakumar

et al. 2021

Sci Rep

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Heat shock proteins contribute to diabetes-induced complications and are affected by glycemic control. Our hypothesis was that hypoglycemia-induced heat shock and related protein changes would be amplified in type 2 diabetes (T2D). This prospective, case–control study enrolled 23 T2D patients and 23 control subjects who underwent hyperinsulinemic-induced hypoglycemia (≤ 2.0 mmol/L (36 mg/dl)) with blood sampling at baseline, at hypoglycemia and after a 24-h post-hypoglycemia follow-up period. Proteomic analysis of heat shock-related and pro-inflammatory proteins was performed. At baseline, MAPKAPK5 (p = 0.02) and UBE2G2 (p = 0.003) were elevated and STUB1 decreased (p = 0.007) in T2D. At hypoglycemia: PPP3CA (p < 0.03) was increased and EPHA2 (p = 0.01) reduced in T2D; by contrast, three proteins were reduced in controls [HSPA1A (p = 0.007), HSPB1 (p < 0.02), SMAD3 (p = 0.005)] while only MAPKAPK5 was elevated (p = 0.02). In the post-hypoglycemia follow-up period, most proteins normalized to baseline by 24-h; however, STIP1 (p = 0.003), UBE2N (p = 0.004) and UBE2L3 (p < 0.04) were decreased in controls at 24-h. No protein differed from baseline at 24-h in T2D. Pro-inflammatory interleukin-6 increased at 4-h post-hypoglycemia in controls and T2D (p < 0.05 and p < 0.003, respectively) and correlated with HSPA1A; anti-inflammatory IL-10 decreased 2-h post-hypoglycemia in T2D only. Other pro-inflammatory proteins, IL-1α, IFN-γ and TNF-α, were unchanged. Heat shock and related proteins differed at baseline between T2D and controls, with an exaggerated response of heat shock and related proteins to hypoglycemia that returned to baseline, though with changes at 24-h in controls alone. An increase in pro-inflammatory IL-6, with a decrease in anti-inflammatory IL-10, suggests that the HSP system is overactivated due to underlying inflammation in T2D.Trial registration: ClinicalTrials.gov NCT03102801.

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Section: Discussionmentioning

confidence: 99%

Impact of severe hypoglycemia on the heat shock and related protein response

Atkin

Moin

Nandakumar

et al. 2021

Sci Rep

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“…Inability of retinal cells to cope with ER stress caused by abnormal protein aggregation or dysfunction of key proteins involved in this process can be considered as a mechanism for the development of ophthalmic diseases. 106 Malfunction of key ER stress signaling proteins was shown to be associated with retinal pathology. For instance, mutations in ER stress sensor gene ATF6 lead to age-dependent degradation of photoreceptors in both humans 107 and mice.…”

Section: Endoplasmic Reticulum Stressmentioning

confidence: 99%

Retinal Damage in Amyotrophic Lateral Sclerosis: Underlying Mechanisms

Солдатов

Kukharsky

Белых

et al. 2021

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease resulting in a gradual loss of motor neuron function. Although ophthalmic complaints are not presently considered a classic symptom of ALS, retinal changes such as thinning, axonal degeneration and inclusion bodies have been found in many patients. Retinal abnormalities observed in postmortem human tissues and animal models are similar to spinal cord changes in ALS. These findings are not dramatically unexpected because retina shares an ontogenetic relationship with the brain, and many genes are associated both with neurodegeneration and retinal diseases. Experimental studies have demonstrated that ALS affects many "vulnerable points" of the retina. Aggregate deposition, impaired nuclear protein import, endoplasmic reticulum stress, glutamate excitotoxicity, vascular regression, and mitochondrial dysfunction are factors suspected as being the main cause of motor neuron damage in ALS. Herein, we show that all of these pathways can affect retinal cells in the same way as motor neurons. Furthermore, we suppose that understanding the patterns of neuro-ophthalmic interaction in ALS can help in the diagnosis and treatment of this disease.

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