Tänään etsin Sars-2 viruksen proteiini-proteiini- interaktioproteiinien (ppi) joukosta niitä, joissa on sinkkiä vativa rakenne.
Näissä on mm. ROC1,joka on RNF75, RING-BOX-1 yhdeltä nimeltään. Tämä sinkkiä vaativa proteiinikomponentti kuuluu CUL5- E3-ubikitiiniligaasirakenteeseen (VACM). ROC1 tekee interaktion Sars-2 viruksen Orf10-tekijään. CUL5 kompleksi aktivoituu vasopressiinillä ja siksi on myös nimi VAMP. Tästä johtui mieleeni,että katson onko vasopressiinipitoisuuksilla jotain assosiaatiota Covid-19 vakavuusasteeseen. Löysin tämän artikkelin:Sars-2 pneumoniaan menehtyneillä on nelinkertaiset Vasopressiinipitoisuudet verrattuna niihin henkilöihin, jotka pysyvät eloissa. Muta toisaalta muissakin pneumonioissa on nousua vasopressiinillä, joten ilmiötä ei katsota ainutlaatuiseksi tunnusmerkiksi Covidille.
Lisätiotetoja VACM signalointijärjestelmästä vasopressiinillä ja CUL5 substraateista kuvan kanssa löytyy linkistä: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812663/ Kuvassa mainitaan usea tekijä, johon Sars-2 tekee interaktiota: Elongiinit, Elongiini B ja Elongiini C ( interaktiotekijä ORF10) Rbx2, Rbx1 ( interaktiotekijäORF10) ja NEDD4/NDFIP2 ( interaktiotekijä Orf9c.
C-peptide [26, 27], the product of the cleavage of proinsulin, is a peptide hormone that acts through a G protein-coupled membrane receptor [28–30]. Given that C-peptide and vasopressin share similar intracellular effects, including the activation of calcium influx and endothelial nitric oxide (NO) synthase [31–36], the effect of C-peptide on Cul5 was examined [37]. Cul5 expression was increased by C-peptide, and the induction was prevented by pertussis toxin, a specific inhibitor of G proteins [37].
https://pubmed.ncbi.nlm.nih.gov/34056499/
Sitaatti 17.12.2021
Activation of Vasopressin System During COVID-19 is Associated With Adverse Clinical Outcomes: An Observational Study
- PMID: 34056499
- PMCID: PMC7989362
- DOI: 10.1210/jendso/bvab045
Background: Activation of the vasopressin system plays a key role for the maintenance of osmotic, cardiovascular, and stress hormone homeostasis during disease. We investigated levels of copeptin, the C-terminal segment of the vasopressin prohormone, that mirrors the production rate of vasopressin in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We measured levels of copeptin on admission and after days 3/4, 5/6, and 7/8 in 74 consecutive hospitalized adult COVID-19 patients and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and acute or chronic bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality.Results: Median admission copeptin levels in COVID-19 patients were almost 4-fold higher in nonsurvivors compared with survivors (49.4 pmol/L [iterquartile range (IQR) 24.9-68.9 pmol/L] vs 13.5 pmol/L [IQR 7.0-26.7 pmol/L]), resulting in an age- and gender-adjusted odds ratio of 7.0 (95% confidence interval [CI] 1.2-40.3), p < 0.03 for mortality. Higher copeptin levels in nonsurvivors persisted during the short-term follow-up. Compared with the control group patients with acute/chronic bronchitis and pneumonia, COVID-19 patients did not have higher admission copeptin levels.Conclusions: A pronounced activation of the vasopressin system in COVID-19 patients is associated with an adverse clinical course in COVID-19 patients. This finding, however, is not unique to COVID-19 but similar to other types of respiratory infections. Keywords: 30-day mortality; COVID-19; SARS-CoV-2; biomarker; copeptin; prognostic markers.
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.
Sitaatti 2. Asiasta on uudempikin artikkeli syyskuulta 2021 ja otan sen tähän jatkoksi:
https://pubmed.ncbi.nlm.nih.gov/34543987/
Epub 2021 Sep 15.
Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective
- PMID: 34543987
- PMCID: PMC8440235
- DOI: 10.1016/j.biopha.2021.112193
In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes.Therefore, this present study aimed to find the potential association between AVP serum level and inflammatory disorders in Covid-19. It has been observed by different recent studies that physiological response due to fever, pain, hypovolemia, dehydration, and psychological stress is characterized by activation release of AVP to counter-balance high blood viscosity in Covid-19 patients. In addition, activated immune cells mainly T and B lymphocytes and released pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells, which in a vicious cycle trigger release of pro-inflammatory cytokines. Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit AVP-induced hyponatremia and release of pro-inflammatory cytokines in Covid-19. In conclusion, release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons. In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines. Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia.
Keywords: Arginine vasopressin; Covid-19; Hyponatremia.Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
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