Endoplasmic Reticulum Stress and Oxidative Stress in Inflammatory Diseases

Tang, Yun; Zhou, Xiangping; Cao, Ting; Chen, En; Li, Yumeng; Lei, Wenbo; Hu, Yibao; He, Bisha; Liu, Shuangquan

doi:10.1089/dna.2022.0353

Cited by 35 publications

(17 citation statements)

References 110 publications

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“…The ER is an important site for regulating protein synthesis, modification, and transport in eukaryotic cells. When unfolded or misfolded proteins accumulate excessively in the ER can cause ER stress and trigger the unfolded protein response(UPR) when triggered 26 . The UPR transmits information about the folding status of proteins in the lumen of the ER to the nucleus and cytoplasm of the cell to reduce the misfolded proteins and unfolded proteins in the ER, thereby maintaining ER homeostasis 27 .…”

Section: Discussionmentioning

confidence: 99%

Potential targets for the treatment of MI: GRP75-mediated Ca²⁺transfer in MAM

Zhang,

Liu,

Sheng

et al. 2023

Preprint

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Background: After myocardial infarction (MI), there is a notable disruption in cellular calcium ion homeostasis and mitochondrial function. These alterations are believed to be linked to endoplasmic reticulum (ER) stress, though the specific mechanisms are not fully understood. This research endeavors to elucidate the involvement of glucose regulated protein 75 (GRP75) in post-MI calcium ion homeostasis and mitochondrial function. Results: Excessive oxidative stress was activated in humans' post-myocardial infarction, with most differentially expressed genes being enriched in metabolic pathways, especially the calcium signaling pathway. In MI rats, symptoms of myocardial injury were accompanied by an increase in the activation of PERK, ATF6, and IRE1, as well as elevated Binding immunoglobulin protein (Bip) expression. Moreover, in oxygen-glucose deprivation (OGD)-induced cardiomyocytes, it was confirmed that inhibiting PERK exacerbated intracellular Ca2+ disruption and cell apoptosis. More importantly, in cardiomyocytes undergoing Tunicamycin-induced ER stress, Ca2+ accumulated in both the ER and mitochondria. Concurrently, the co-localization of GRP75 with IP3R and VDAC1 increased under ER stress in cardiomyocytes. In OGD-induced cardiomyocytes, knockdown of GRP75 not only reduced the Ca2+ levels in both the ER and mitochondria and improved the ultrastructure of cardiomyocytes, but it also increased the number of contact points between ER and mitochondria, reducing MAM formation, and decreased cell apoptosis. Significantly, knockdown of GRP75 did not affect the protein expression of PERK and hypoxia-inducible factor 1α (HIF-1α). Transcriptome analysis of cardiomyocytes revealed that knockdown of GRP75 mainly influenced the molecular functions of sialyltransferase and IP3R, as well as the biosynthesis of glycosphingolipids and lactate metabolism. In OGD-induced cardiomyocytes, the knockdown of GRP75 lowered the protein expression levels of glucose transporter-1 (Glut1), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA), and decreased the metabolic products of glycolysis. Conclusion: The complex interaction between the ER and mitochondria, driven by the GRP75 and its associated IP3R1-GRP75-VDAC1 complex, is crucial for calcium homeostasis and cardiomyocyte's adaptive response to ER stress. Modulating GRP75 could offer a strategy to regulate calcium dynamics, diminish glycolysis, and thereby mitigate cardiomyocyte apoptosis.

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Section: Discussionmentioning

confidence: 99%

Potential targets for the treatment of MI: GRP75-mediated Ca²⁺transfer in MAM

Zhang,

Liu,

Sheng

et al. 2023

Preprint

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“…Moreover, increasing studies have suggested that oxidative stress occupies an important role in the progression of these inflammatory diseases. 119 The main medications used currently to treat inflammatory diseases include steroids, non-steroidal anti-inflammatory drugs, and immunosuppressants. The use of these traditional drugs, although effective, tended to cause some unnecessary side effects, such as hemolytic anemia and osteoporosis.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Protein-guided biomimetic nanomaterials: a versatile theranostic nanoplatform for biomedical applications

Zhang,

Pan,

Chen

et al. 2024

Nanoscale

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“…25 Oxidative stress and ER stress coexist in a variety of physiological states and can interact. 33 The formation of disulfide bonds in the ER is very sensitive to changes in redox equilibrium. 34 The pro-oxidant effects can disrupt the normal protein folding process, resulting in ER stress, and then induce the production of ROS in the ER and mitochondria (Fig.…”

Section: Papermentioning

confidence: 99%