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ERC-BiP Functional Protein Pathway for Assessing Endoplasmic Reticulum Stress Induced by SARS-CoV-2 Replication after
Mingshan Xue1,2,3, Zhiwei Lin3, Teng Zhang4,5
1Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou 510060, China.
Background:
SARS-CoV-2 induces apoptosis and amplifies the immune response by continuously stressing the endoplasmic reticulum (ER) after invading cells. This study aimed to establish a protein-metabolic pathway associated with ER dysfunction based on the invasion mechanism of SARS-CoV-2.
Methods:
This study included 17 healthy people and 46 COVID-19 patients, including 38 mild patients and 8 severe patients. Proteomics and metabolomics were measured in the patient plasma collected at admission and one week after admission. The patients were further divided into the aggravation and remission groups based on disease progression within one week of admission.
Results:
Cross-sectional comparison showed that endoplasmic reticulum molecular chaperone-binding immunoglobulin protein (ERC-BiP), angiotensinogen (AGT), ceramide acid (Cer), and C-reactive protein (CRP) levels were significantly increased in COVID-19 patients, while the sphingomyelin (SM) level was significantly decreased (P < 0.05). In addition, longitudinal comparative analysis found that the temporal fold changes of ERC-BiP, AGT, Cer, CRP, and SM were significantly different between the patients in the aggravation and remission groups (P < 0.05). ERC-BiP, AGT, and Cer levels were significantly increased in aggravation patients, while SM was significantly decreased (P < 0.05). Meanwhile, ERC-BiP was significantly correlated with AGT (r = 0.439; P < 0.001).
Conclusions:
ERC-BiP can be used as a core index to reflect the degree of ER stress in COVID-19 patients, which is of great value for evaluating the functional state of cells. A functional pathway for AGT/ERC-BiP/glycolysis can directly assess the activation of unfolded protein reactions. The ERC-BiP pathway is closer to the intracellular replication pathway of SARS-CoV-2 and may help in the development of predictive protocols for COVID-19 exacerbation.
Insights
SARS-CoV-2 infection causes endoplasmic reticulum (ER) stress, identified by elevated ERC-BiP, AGT, and Cer levels and decreased SM. This protein-metabolic pathway aids in predicting COVID-19 severity.
Area of Science:
- Biochemistry
- Immunology
- Virology
Background:
- SARS-CoV-2 invades cells, inducing apoptosis and immune responses via endoplasmic reticulum (ER) stress.
- Understanding the protein-metabolic pathways linked to ER dysfunction is crucial for COVID-19 research.
Purpose of the Study:
- To establish a protein-metabolic pathway associated with ER dysfunction in SARS-CoV-2 infection.
- To identify biomarkers for predicting COVID-19 progression.
Main Methods:
- Proteomics and metabolomics analysis of plasma from 17 healthy individuals and 46 COVID-19 patients (38 mild, 8 severe).
- Patients were categorized into aggravation and remission groups based on disease progression within one week.
- Longitudinal and cross-sectional analyses were performed to compare biomarker levels.
Main Results:
- COVID-19 patients showed significantly increased levels of ERC-BiP, AGT, Cer, and CRP, and decreased SM compared to healthy controls.
- Patients who aggravated had higher ERC-BiP, AGT, and Cer, and lower SM levels than those in remission.
- ERC-BiP was significantly correlated with AGT.
Conclusions:
- ERC-BiP serves as a key indicator of ER stress in COVID-19 patients, valuable for assessing cellular function.
- The AGT/ERC-BiP/glycolysis pathway can assess unfolded protein reactions.
- The ERC-BiP pathway's proximity to SARS-CoV-2 replication suggests its potential in developing predictive protocols for COVID-19 exacerbation.
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