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Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması

Yıl 2021, Cilt: 47 Sayı: 1, 17 - 22, 01.04.2021
https://doi.org/10.32708/uutfd.858821

Öz

GRP-78 proteininin bat koronavirüs, Mers-Cov, ebola virüs, deng virüsü, japon ensefalit virüsü, influenza virüs ve zika virüs gibi birçok virüsün hücreye girişinde rol oynadığı bilinmektedir. Bu çalışmada COVID-19 enfeksiyonu geçirmiş ve tedavi almış ve tamamen iyileşmiş olan hastalarda tedavi başlangıcından üç ay sonrasındaki Glucose Regulated Protein-78 (GRP-78) düzeylerini incelemeyi amaçladık. Daha öncesinde Sabırlı ve ark. tarafından yapılan çalışma grubunda yer alan, COVID-19 hastalığı tanısı almış ve hastalığı geçirip tamamen iyileşmiş olan 20 hasta prospektif kohorta dahil edildi. Hastaların acil servise ilk tanıda başvurusu ve 3 ay sonra kontrole çağrıldığında alınan kanlardan enzyme-linked immunosorbent assay (ELISA) metodu ile GRP-78 düzeyi çalışıldı. Acil servise ilk başvuruda alınan kanda serum GRP-78 düzeyi 1393,31 ± 306,33 pg/ml; tedavi başlangıcından 90 gün sonra bakılan serum GRP-78 düzeyi ise 1451,73 ± 336,65 pg/ml olarak saptandı. İlk başvuru ve 3 ay sonraki kontrolde ölçülen GRP-78 düzeyleri açısından istatistiksel olarak anlamlı farklılık saptanmadı (p=0,451). Sonuç olarak bu çalışmada COVID-19 infeksiyonunda tedavi başlangıcından 3 ay sonrasında dahi yüksek seyrettiğini ortaya koyduk. GRP-78 düzeyinin yüksek kalmasının kişinin Sars-CoV-2 virüsüne karşı immunitesi konusunda fikir verdirici olabilir fakat bu hususun gerek hücre kültürü çalışması ve gerekse daha uzun süreli kohort çalışması yapılarak incelenmesine ihtiyaç vardır.

Kaynakça

  • 1- CDC. 2019 Novel Coronavirus, Wuhan, China. CDC. Available at https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. January 26, 2020; Accessed: January 27, 2020. Gallegos A. WHO Declares Public Health Emergency for Novel Coronavirus. Medscape Medical News. Available at https://www.medscape.com/viewarticle/924596. January 30, 2020; Son Erişim Tarihi:1 Aralık, 2020.)
  • 2- Cascella M, Rajnik M, Cuomo A, et al. Features, Evaluation, and Treatment of Coronavirus (COVID-19) [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/
  • 3- Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020;5: 536–44.
  • 4- Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41:1141-9.
  • 5- Kuo L, Godeke GJ, Raamsman MJ, Masters PS, Rottier PJ. Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: crossing the host cell species barrier. J Virol 2000;74: 1393-1406.
  • 6- Yamada Y, Liu XB, Fang SG, Tay FP, Liu DX. Acquisition of cell-cell fusion activity by amino acid substitutions in spike protein determines the infectivity of a coronavirus in cultured cells. PLoS One 2009;4:e6130.
  • 7- Zhang Y, Liu R, Ni M, Gill P, Lee AS. Cell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiP. J Biol Chem. 2010;14;285:15065-75.
  • 8- Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: A cell's response to stress. Life Sci. 2019;226:156-63.
  • 9- Chu H, Chan CM, Zhang X, et al. Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells. J J Biol Chem. 2018;293:11709-26.
  • 10- Köseler A, Sabirli R, Gören T, Türkçüer I, Kurt Ö. Endoplasmic Reticulum Stress Markers in SARS-COV-2 Infection and Pneumonia: Case-Control Study. In Vivo. 2020;34:1645-50.
  • 11- Palmeira A, Sousa E, Köseler A, et al. Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection. Pharmaceuticals (Basel). 2020;13:132.
  • 12- Sabirli R, Koseler A, Goren T, Turkcuer I, Kurt O. High GRP78 levels in Covid-19 infection: A case-control study. Life Sci. 2021;265:118781.
  • 13- https://covid19.saglik.gov.tr/Eklenti/39061/0/covid19rehberieriskinhastatedavisipdf.pdf. (Son Erişim Tarihi:11.12.2020)
  • 14- Chan CP, Siu KL, Chin KT, Yuen KY, Zheng B, Jin DY. Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2006;80:9279-87.
  • 15- Versteeg GA, van de Nes PS, Bredenbeek PJ, Spaan WJ. The Coronavirus Spike Protein Induces Endoplasmic Reticulum Stress and Upregulation of Intracellular Chemokine mRNA Concentrations. J Virol. 2007; 81: 10981-90.
  • 16- Doerflinger M, Reljic B, Menassa J, et al. Circulating BiP/Grp78 is a novel prognostic marker for sepsis-mediated immune cell death. FEBS J. 2020 Sep 7. doi: 10.1111/febs.15552. Epub ahead of print. PMID: 32894892.
  • 17- Stan RC, Pinto Bonin C, Porto R, Soriano FG, de Camargo MM. Increased grp78 transcription is correlated to reduced tlr4 transcription in patients surviving sepsis. Clin Exp Immunol. 2019;198:273-80.
  • 18- Ma Y, Yu J, Chan HL, et al. Glucose-regulated protein 78 is an intracellular antiviral factor against hepatitis B virus. Mol Cell Proteomics. 2009;8:2582-94.

Serum GRP-78 Levels Still Remain High 3 Months Later After the Treatment: A Cohort Study

Yıl 2021, Cilt: 47 Sayı: 1, 17 - 22, 01.04.2021
https://doi.org/10.32708/uutfd.858821

Öz

Glucose Regulated Protein (GRP-78) plays a role in the intrusion of many viruses such as bat coronavirus, MERS-CoV, ebola virus, dengue virus, Japanese encephalitis virus, influenza virus, and Zika virus. This study, however, aims to examine the GRP-78 levels in patients who were infected with COVID-19, treated and recovered completely three months after the initiation of treatment. A total of 20 patients who were diagnosed with the COVID-19 disease and fully recovered, and who had participated in a previous study conducted by Sabırlı et al., were included in this prospective cohort study. Using the enzyme-linked immunosorbent assay (ELISA) method, the GRP-78 levels were examined in the blood samples. The mean serum GRP-78 level was found to be 1393.31 ± 306.33 pg / ml in the blood samples drawn from the patients when they were first admitted to the emergency department while the mean serum GRP-78 level measured 90 days after the initiation of treatment was 1451.73 ± 336.65 pg / ml. No statistically significant differences were found between the GRP-78 levels measured during the first admission and the follow-up control 3 months later (p = 0.451). In conclusion, this study revealed that the GRP-78 levels remained high in patients with COVID-19 infections even after 3 months following the initiation of treatment. This high GRP-78 level may provide insight into the immunity of the person against the Sars-CoV-2 virus; however, this issue should be further examined both in a cell culture study and in a longer-term cohort study.

Kaynakça

  • 1- CDC. 2019 Novel Coronavirus, Wuhan, China. CDC. Available at https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. January 26, 2020; Accessed: January 27, 2020. Gallegos A. WHO Declares Public Health Emergency for Novel Coronavirus. Medscape Medical News. Available at https://www.medscape.com/viewarticle/924596. January 30, 2020; Son Erişim Tarihi:1 Aralık, 2020.)
  • 2- Cascella M, Rajnik M, Cuomo A, et al. Features, Evaluation, and Treatment of Coronavirus (COVID-19) [Updated 2020 Aug 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/
  • 3- Coronaviridae Study Group of the International Committee on Taxonomy of Viruses. The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nat. Microbiol. 2020;5: 536–44.
  • 4- Huang Y, Yang C, Xu XF, Xu W, Liu SW. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41:1141-9.
  • 5- Kuo L, Godeke GJ, Raamsman MJ, Masters PS, Rottier PJ. Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: crossing the host cell species barrier. J Virol 2000;74: 1393-1406.
  • 6- Yamada Y, Liu XB, Fang SG, Tay FP, Liu DX. Acquisition of cell-cell fusion activity by amino acid substitutions in spike protein determines the infectivity of a coronavirus in cultured cells. PLoS One 2009;4:e6130.
  • 7- Zhang Y, Liu R, Ni M, Gill P, Lee AS. Cell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiP. J Biol Chem. 2010;14;285:15065-75.
  • 8- Ibrahim IM, Abdelmalek DH, Elfiky AA. GRP78: A cell's response to stress. Life Sci. 2019;226:156-63.
  • 9- Chu H, Chan CM, Zhang X, et al. Middle East respiratory syndrome coronavirus and bat coronavirus HKU9 both can utilize GRP78 for attachment onto host cells. J J Biol Chem. 2018;293:11709-26.
  • 10- Köseler A, Sabirli R, Gören T, Türkçüer I, Kurt Ö. Endoplasmic Reticulum Stress Markers in SARS-COV-2 Infection and Pneumonia: Case-Control Study. In Vivo. 2020;34:1645-50.
  • 11- Palmeira A, Sousa E, Köseler A, et al. Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection. Pharmaceuticals (Basel). 2020;13:132.
  • 12- Sabirli R, Koseler A, Goren T, Turkcuer I, Kurt O. High GRP78 levels in Covid-19 infection: A case-control study. Life Sci. 2021;265:118781.
  • 13- https://covid19.saglik.gov.tr/Eklenti/39061/0/covid19rehberieriskinhastatedavisipdf.pdf. (Son Erişim Tarihi:11.12.2020)
  • 14- Chan CP, Siu KL, Chin KT, Yuen KY, Zheng B, Jin DY. Modulation of the unfolded protein response by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2006;80:9279-87.
  • 15- Versteeg GA, van de Nes PS, Bredenbeek PJ, Spaan WJ. The Coronavirus Spike Protein Induces Endoplasmic Reticulum Stress and Upregulation of Intracellular Chemokine mRNA Concentrations. J Virol. 2007; 81: 10981-90.
  • 16- Doerflinger M, Reljic B, Menassa J, et al. Circulating BiP/Grp78 is a novel prognostic marker for sepsis-mediated immune cell death. FEBS J. 2020 Sep 7. doi: 10.1111/febs.15552. Epub ahead of print. PMID: 32894892.
  • 17- Stan RC, Pinto Bonin C, Porto R, Soriano FG, de Camargo MM. Increased grp78 transcription is correlated to reduced tlr4 transcription in patients surviving sepsis. Clin Exp Immunol. 2019;198:273-80.
  • 18- Ma Y, Yu J, Chan HL, et al. Glucose-regulated protein 78 is an intracellular antiviral factor against hepatitis B virus. Mol Cell Proteomics. 2009;8:2582-94.
Toplam 18 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Acil Tıp, Bulaşıcı Hastalıklar
Bölüm Özgün Araştırma Makaleleri
Yazarlar

Ramazan Sabırlı 0000-0003-4599-5833

Aylin Köseler 0000-0003-4832-0436

Tarık Gören Bu kişi benim 0000-0002-8292-6717

Aykut Kemancı 0000-0002-6308-3830

Neslihan Türkçüer Bu kişi benim 0000-0002-2029-8751

İbrahim Türkçüer 0000-0001-8342-4615

Özgür Kurt 0000-0001-5575-588X

Yayımlanma Tarihi 1 Nisan 2021
Kabul Tarihi 12 Şubat 2021
Yayımlandığı Sayı Yıl 2021 Cilt: 47 Sayı: 1

Kaynak Göster

APA Sabırlı, R., Köseler, A., Gören, T., Kemancı, A., vd. (2021). Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması. Uludağ Üniversitesi Tıp Fakültesi Dergisi, 47(1), 17-22. https://doi.org/10.32708/uutfd.858821
AMA Sabırlı R, Köseler A, Gören T, Kemancı A, Türkçüer N, Türkçüer İ, Kurt Ö. Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması. Uludağ Tıp Derg. Nisan 2021;47(1):17-22. doi:10.32708/uutfd.858821
Chicago Sabırlı, Ramazan, Aylin Köseler, Tarık Gören, Aykut Kemancı, Neslihan Türkçüer, İbrahim Türkçüer, ve Özgür Kurt. “Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 47, sy. 1 (Nisan 2021): 17-22. https://doi.org/10.32708/uutfd.858821.
EndNote Sabırlı R, Köseler A, Gören T, Kemancı A, Türkçüer N, Türkçüer İ, Kurt Ö (01 Nisan 2021) Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması. Uludağ Üniversitesi Tıp Fakültesi Dergisi 47 1 17–22.
IEEE R. Sabırlı, A. Köseler, T. Gören, A. Kemancı, N. Türkçüer, İ. Türkçüer, ve Ö. Kurt, “Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması”, Uludağ Tıp Derg, c. 47, sy. 1, ss. 17–22, 2021, doi: 10.32708/uutfd.858821.
ISNAD Sabırlı, Ramazan vd. “Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi 47/1 (Nisan 2021), 17-22. https://doi.org/10.32708/uutfd.858821.
JAMA Sabırlı R, Köseler A, Gören T, Kemancı A, Türkçüer N, Türkçüer İ, Kurt Ö. Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması. Uludağ Tıp Derg. 2021;47:17–22.
MLA Sabırlı, Ramazan vd. “Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması”. Uludağ Üniversitesi Tıp Fakültesi Dergisi, c. 47, sy. 1, 2021, ss. 17-22, doi:10.32708/uutfd.858821.
Vancouver Sabırlı R, Köseler A, Gören T, Kemancı A, Türkçüer N, Türkçüer İ, Kurt Ö. Serum GRP-78 Düzeyleri Tedaviden 3 Ay Sonrasında Halen Yüksek Seyretmektedir: Bir Kohort Çalışması. Uludağ Tıp Derg. 2021;47(1):17-22.

ISSN: 1300-414X, e-ISSN: 2645-9027

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