Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis

Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous stud...

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Main Authors: Philma Glora Muthuraj, Aryamav Pattnaik, Prakash K. Sahoo, Md Torikul Islam, Asit K. Pattnaik, Siddappa N. Byrareddy, Corrine Hanson, Ann Anderson Berry, Stephen D. Kachman, Sathish Kumar Natarajan
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/9/6/643
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author Philma Glora Muthuraj
Aryamav Pattnaik
Prakash K. Sahoo
Md Torikul Islam
Asit K. Pattnaik
Siddappa N. Byrareddy
Corrine Hanson
Ann Anderson Berry
Stephen D. Kachman
Sathish Kumar Natarajan
author_facet Philma Glora Muthuraj
Aryamav Pattnaik
Prakash K. Sahoo
Md Torikul Islam
Asit K. Pattnaik
Siddappa N. Byrareddy
Corrine Hanson
Ann Anderson Berry
Stephen D. Kachman
Sathish Kumar Natarajan
author_sort Philma Glora Muthuraj
collection DOAJ
description Zika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted in apoptosis and treatment of palmitoleate to ZIKV-infected cells significantly prevented apoptosis. However, palmitate (saturated fatty acid) did not offer protection from ZIKV-induced ER stress and apoptosis. We also observed that the Zika viral RNA copies were decreased, and the cell viability improved in ZIKV-infected cells treated with palmitoleate as compared to the infected cells without palmitoleate treatment. Further, palmitoleate was shown to protect against ZIKV-induced upregulation of ER stress markers, C/EBP homologous protein and X-box binding protein-1 splicing in placental trophoblasts. In conclusion, our studies suggest that palmitoleate protects placental trophoblasts against ZIKV-induced ER stress and apoptosis.
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spelling doaj.art-bc532a1c34e445f5beb6f8063cea21572023-11-21T22:53:27ZengMDPI AGBiomedicines2227-90592021-06-019664310.3390/biomedicines9060643Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast ApoptosisPhilma Glora Muthuraj0Aryamav Pattnaik1Prakash K. Sahoo2Md Torikul Islam3Asit K. Pattnaik4Siddappa N. Byrareddy5Corrine Hanson6Ann Anderson Berry7Stephen D. Kachman8Sathish Kumar Natarajan9Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USANebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USANebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, USAChild Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USAChild Health Research Institute, University of Nebraska Medical Center, Omaha, NE 68198, USADepartment of Statistics, University of Nebraska-Lincoln, Lincoln, NE 68583, USADepartment of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USAZika virus (ZIKV) infection in pregnancy is associated with the development of microcephaly, intrauterine growth restriction, and ocular damage in the fetus. ZIKV infection of the placenta plays a crucial role in the vertical transmission from the maternal circulation to the fetus. Our previous study suggested that ZIKV induces endoplasmic reticulum (ER) stress and apoptosis of placental trophoblasts. Here, we showed that palmitoleate, an omega-7 monounsaturated fatty acid, prevents ZIKV-induced ER stress and apoptosis in placental trophoblasts. Human trophoblast cell lines (JEG-3 and JAR) and normal immortalized trophoblasts (HTR-8) were used. We observed that ZIKV infection of the trophoblasts resulted in apoptosis and treatment of palmitoleate to ZIKV-infected cells significantly prevented apoptosis. However, palmitate (saturated fatty acid) did not offer protection from ZIKV-induced ER stress and apoptosis. We also observed that the Zika viral RNA copies were decreased, and the cell viability improved in ZIKV-infected cells treated with palmitoleate as compared to the infected cells without palmitoleate treatment. Further, palmitoleate was shown to protect against ZIKV-induced upregulation of ER stress markers, C/EBP homologous protein and X-box binding protein-1 splicing in placental trophoblasts. In conclusion, our studies suggest that palmitoleate protects placental trophoblasts against ZIKV-induced ER stress and apoptosis.https://www.mdpi.com/2227-9059/9/6/643monounsaturated fatty acidsendoplasmic reticulum stressapoptosisviral replicationZika virusplacenta
spellingShingle Philma Glora Muthuraj
Aryamav Pattnaik
Prakash K. Sahoo
Md Torikul Islam
Asit K. Pattnaik
Siddappa N. Byrareddy
Corrine Hanson
Ann Anderson Berry
Stephen D. Kachman
Sathish Kumar Natarajan
Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis
Biomedicines
monounsaturated fatty acids
endoplasmic reticulum stress
apoptosis
viral replication
Zika virus
placenta
title Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis
title_full Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis
title_fullStr Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis
title_full_unstemmed Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis
title_short Palmitoleate Protects against Zika Virus-Induced Placental Trophoblast Apoptosis
title_sort palmitoleate protects against zika virus induced placental trophoblast apoptosis
topic monounsaturated fatty acids
endoplasmic reticulum stress
apoptosis
viral replication
Zika virus
placenta
url https://www.mdpi.com/2227-9059/9/6/643
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