A Pilot Study on Blood Components in COVID-19 Affected Subjects: A Correlation to UPR Signalling and ER-Stress.

IF 1.5 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Indian Journal of Clinical Biochemistry Pub Date : 2023-07-01 DOI:10.1007/s12291-023-01121-8
Akash Bansal, Sushil Kumar, Neha Rai, Shilpi Kumari, Visesh Kumar, Ajeet Kumar, Nimai Chand Chandra
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Abstract

Abstract: The endoplasmic reticulum (ER) is the site for protein synthesis, its folding and secretion. An intricate set of signalling pathways, called UPR pathways, have been evolved by ER in mammalian cells, to allow the cell to respond the presence of misfolded proteins within the ER. Breaching of these signalling systems by disease oriented accumulation of unfolded proteins may develop cellular stress. The aim of this study is to explore whether COVID-19 infection is responsible for developing this kind of endoplasmic reticulum related stress (ER-stress). ER-stress was evaluated by checking the expression of ER-stress markers e.g. PERK (adapting) and TRAF2 (alarming). ER-stress was correlated to several blood parameters viz. IgG, pro- and anti-inflammatory cytokines, leukocytes, lymphocytes, RBC, haemoglobin and PaO2/FiO2 ratio (ratio of arterial oxygen partial pressure to fractional inspired oxygen) in COVID-19 affected subjects. COVID-19 infection was found to be a state of protein homeostasis (proteostasis) collapse. Changes in IgG levels showed very poor immune response by the infected subjects. At the initial phase of the disease, pro-inflammatory cytokine levels were high and anti-inflammatory cytokines levels were low; though they were partly compromised at later phase of the disease. Total leukocyte concentration increased over the period of time; while percentage of lymphocytes were dropped. No significant changes were observed in cases of RBC counts and haemoglobin (Hb) levels. Both RBC and Hb were maintained at their normal range. In mildly stressed group, PaO2/FiO2 ratio (oxygenation status) was in the higher side of normal range; whereas in other two groups the ratio was in respiratory distress syndrome mode. Virus could induce mild to severe ER-stress, which could be the cause of cellular death and systemic dysfunction introducing fatal consequences.

Graphical abstract: Schematic representation of SARS-CoV-2 infection and related consequences.

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新冠肺炎患者血液成分与UPR信号和er应激的相关性研究
摘要:内质网(ER)是蛋白质合成、折叠和分泌的场所。哺乳动物细胞中的内质网进化出了一套复杂的信号通路,称为UPR通路,使细胞能够对内质网中错误折叠的蛋白质做出反应。通过疾病导向的未折叠蛋白积累破坏这些信号系统可能会产生细胞应激。本研究旨在探讨COVID-19感染是否导致了这种内质网相关应激(ER-stress)的发生。通过检测内质网应激标志物如PERK(适应)和TRAF2(报警)的表达来评估内质网应激。内质网应激与COVID-19患者的IgG、促炎性和抗炎性细胞因子、白细胞、淋巴细胞、红细胞、血红蛋白和PaO2/FiO2比值(动脉氧分压与分次吸入氧的比值)相关。COVID-19感染被发现是一种蛋白质稳态(proteostasis)崩溃的状态。IgG水平的变化表明受感染者的免疫反应非常差。在疾病初期,促炎细胞因子水平高,抗炎细胞因子水平低;尽管它们在疾病后期部分受损。白细胞总浓度随时间增加;淋巴细胞百分比下降。红细胞计数和血红蛋白(Hb)水平未见明显变化。红细胞和血红蛋白均维持在正常范围。轻度应激组PaO2/FiO2比值(氧合状态)在正常范围偏高;而其他两组均处于呼吸窘迫综合征模式。病毒可引起轻度至重度内质网应激,这可能是导致细胞死亡和系统功能障碍的致命后果的原因。图形摘要:SARS-CoV-2感染示意图及相关后果。
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来源期刊
Indian Journal of Clinical Biochemistry
Indian Journal of Clinical Biochemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
4.50
自引率
4.80%
发文量
74
期刊介绍: The primary mission of the journal is to promote improvement in the health and well-being of community through the development and practice of clinical biochemistry and dissemination of knowledge and recent advances in this discipline among professionals, diagnostics industry, government and non-government organizations. Indian Journal of Clinical Biochemistry (IJCB) publishes peer reviewed articles that contribute to the existing knowledge in all fields of Clinical biochemistry, either experimental or theoretical, particularly deal with the applications of biochemistry, molecular biology, genetics, biotechnology, and immunology to the diagnosis, treatment, monitoring and prevention of human diseases. The articles published also include those covering the analytical and molecular diagnostic techniques, instrumentation, data processing, quality assurance and accreditation aspects of the clinical investigations in which chemistry has played a major role, or laboratory animal studies with biochemical and clinical relevance.
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