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Article ; Online: ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection.

Eng, Margaret E / Imperio, Guinever E / Bloise, Enrrico / Matthews, Stephen G

Cellular and molecular life sciences : CMLS

2022 Volume 79, Issue 8, Page(s) 415

Abstract: ... to increase expression and function of drug transporters and increase brain protection (e.g., sGC ... brain exposure to xenobiotics (e.g., tumor necrosis factor [TNF], interleukin [IL]-6), negatively ... to agents that target or access the nervous system, such as stimulants (e.g., caffeine), anesthetics (e.g ...

Abstract	The blood-brain barrier (BBB) provides essential neuroprotection from environmental toxins and xenobiotics, through high expression of drug efflux transporters in endothelial cells of the cerebral capillaries. However, xenobiotic exposure, stress, and inflammatory stimuli have the potential to disrupt BBB permeability in fetal and post-natal life. Understanding the role and ability of the BBB in protecting the developing brain, particularly with respect to drug/toxin transport, is key to promoting long-term brain health. Drug transporters, particularly P-gp and BCRP are expressed in early gestation at the developing BBB and have a crucial role in developmental homeostasis and fetal brain protection. We have highlighted several factors that modulate drug transporters at the developing BBB, including synthetic glucocorticoid (sGC), cytokines, maternal infection, and growth factors. Some factors have the potential to increase expression and function of drug transporters and increase brain protection (e.g., sGC, transforming growth factor [TGF]-β). However, others inhibit drug transporters expression and function at the BBB, increasing brain exposure to xenobiotics (e.g., tumor necrosis factor [TNF], interleukin [IL]-6), negatively impacting brain development. This has implications for pregnant women and neonates, who represent a vulnerable population and may be exposed to drugs and environmental toxins, many of which are P-gp and BCRP substrates. Thus, alterations in regulated transport across the developing BBB may induce long-term changes in brain health and compromise pregnancy outcome. Furthermore, a large portion of neonatal adverse drug reactions are attributed to agents that target or access the nervous system, such as stimulants (e.g., caffeine), anesthetics (e.g., midazolam), analgesics (e.g., morphine) and antiretrovirals (e.g., Zidovudine); thus, understanding brain protection is key for the development of strategies to protect the fetal and neonatal brain.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics ; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism ; ATP-Binding Cassette Transporters/metabolism ; Adenosine Triphosphate/metabolism ; Blood-Brain Barrier/metabolism ; Brain/metabolism ; Endothelial Cells/metabolism ; Female ; Humans ; Infant, Newborn ; Interleukin-6/metabolism ; Membrane Transport Proteins/metabolism ; Neoplasm Proteins/metabolism ; Pregnancy ; Xenobiotics/metabolism
Chemical Substances	ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters ; Interleukin-6 ; Membrane Transport Proteins ; Neoplasm Proteins ; Xenobiotics ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2022-07-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04432-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: ATP-binding cassette (ABC) drug transporters in the developing blood-brain barrier: role in fetal brain protection

Eng, Margaret E. / Imperio, Guinever E. / Bloise, Enrrico / Matthews, Stephen G.

Cell. Mol. Life Sci.. 2022 Aug., v. 79, no. 8 p.415-415

2022

Abstract	The blood-brain barrier (BBB) provides essential neuroprotection from environmental toxins and xenobiotics, through high expression of drug efflux transporters in endothelial cells of the cerebral capillaries. However, xenobiotic exposure, stress, and inflammatory stimuli have the potential to disrupt BBB permeability in fetal and post-natal life. Understanding the role and ability of the BBB in protecting the developing brain, particularly with respect to drug/toxin transport, is key to promoting long-term brain health. Drug transporters, particularly P-gp and BCRP are expressed in early gestation at the developing BBB and have a crucial role in developmental homeostasis and fetal brain protection. We have highlighted several factors that modulate drug transporters at the developing BBB, including synthetic glucocorticoid (sGC), cytokines, maternal infection, and growth factors. Some factors have the potential to increase expression and function of drug transporters and increase brain protection (e.g., sGC, transforming growth factor [TGF]-β). However, others inhibit drug transporters expression and function at the BBB, increasing brain exposure to xenobiotics (e.g., tumor necrosis factor [TNF], interleukin [IL]-6), negatively impacting brain development. This has implications for pregnant women and neonates, who represent a vulnerable population and may be exposed to drugs and environmental toxins, many of which are P-gp and BCRP substrates. Thus, alterations in regulated transport across the developing BBB may induce long-term changes in brain health and compromise pregnancy outcome. Furthermore, a large portion of neonatal adverse drug reactions are attributed to agents that target or access the nervous system, such as stimulants (e.g., caffeine), anesthetics (e.g., midazolam), analgesics (e.g., morphine) and antiretrovirals (e.g., Zidovudine); thus, understanding brain protection is key for the development of strategies to protect the fetal and neonatal brain.
Keywords	P-glycoproteins ; antiretroviral agents ; at-risk population ; blood-brain barrier ; brain ; caffeine ; glucocorticoids ; homeostasis ; interleukins ; morphine ; neuroprotective effect ; permeability ; pregnancy outcome ; toxins ; tumor necrosis factors ; xenobiotics
Language	English
Dates of publication	2022-08
Size	p. 415.
Publishing place	Springer International Publishing
Document type	Article ; Online
Note	Review
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-022-04432-w
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Article ; Online: ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth.

Lye, Phetcharawan / Dunk, Caroline E / Zhang, Jianhong / Wei, Yanxing / Nakpu, Jittanan / Hamada, Hirotaka / Imperio, Guinever E / Bloise, Enrrico / Matthews, Stephen G / Lye, Stephen J

Cells

2021 Volume 10, Issue 7

Abstract: COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies ( ...

Abstract	COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies (
MeSH term(s)	Adult ; Angiotensin-Converting Enzyme 2/genetics ; COVID-19/genetics ; COVID-19/transmission ; Female ; Gene Expression ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Lymphocytes/metabolism ; Monocytes/metabolism ; Placenta/cytology ; Placenta/metabolism ; Pregnancy ; Pregnancy Complications, Infectious/genetics ; Premature Birth/etiology ; Premature Birth/genetics ; SARS-CoV-2/isolation & purification
Chemical Substances	ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Language	English
Publishing date	2021-07-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells10071724
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Article ; Online: ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth

Phetcharawan Lye / Caroline E. Dunk / Jianhong Zhang / Yanxing Wei / Jittanan Nakpu / Hirotaka Hamada / Guinever E. Imperio / Enrrico Bloise / Stephen G. Matthews / Stephen J. Lye

Cells, Vol 10, Iss 1724, p

2021 Volume 1724

Abstract	COVID-19 is associated with increased incidence of preterm birth (PTB). We assessed pathways by which SARS-CoV-2 could access the placenta. Placentae, from PTB with or without chorioamnionitis (ChA), or from term pregnancies ( n = 12/13/group) were collected. Peripheral blood was collected from healthy pregnant women ( n = 6). Second trimester placental explants (16–20 weeks, n = 5/group) were treated with lipopolysaccharide (LPS, to mimic bacterial infection) and ACE2, CCL2, IL-6/8 and TNFα mRNA was assessed. ChA-placentae exhibited increased ACE2 and CCL2 mRNA expression ( p < 0.05). LPS increased cytokine and ACE2 mRNA in placental explants. Placental ACE2 protein localized to syncytiotrophoblast, fetal endothelium, extravillous trophoblast and in immune cells-subsets (M1/M2 macrophage and neutrophils) within the villous stroma. Significantly increased numbers of M1 macrophage and neutrophils were present in the ChA-placenta ( p < 0.001). Subsets of peripheral immune cells from pregnant women express the ACE2 mRNA and protein. A greater fraction of granulocytes was positive for ACE2 protein expression compared to lymphocytes or monocytes. These data suggest that in pregnancies complicated by ChA, ACE2 positive immune cells in the maternal circulation have the potential to traffic SARS-CoV-2 virus to the placenta and increase the risk of vertical transmission to the placenta/fetus.
Keywords	SARS-CoV-2 ; COVID-19 ; ACE2 ; chorioamnionitis ; preterm birth ; M1 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Functional Expression of Multidrug-Resistance (MDR) Transporters in Developing Human Fetal Brain Endothelial Cells.

Lye, Phetcharawan / Bloise, Enrrico / Imperio, Guinever E / Chitayat, David / Matthews, Stephen G

Cells

2022 Volume 11, Issue 14

Abstract: There is little information about the functional expression of the multidrug resistance (MDR) transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2) in the developing blood−brain barrier (BBB). We isolated ... ...

Abstract	There is little information about the functional expression of the multidrug resistance (MDR) transporters P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP/ABCG2) in the developing blood−brain barrier (BBB). We isolated and cultured primary human fetal brain endothelial cells (hfBECs) from early and mid-gestation brains and assessed P-gp/ABCB1 and BCRP/ABCG2 expression and function, as well as tube formation capability. Immunolocalization of the von Willebrand factor (marker of endothelial cells), zonula occludens-1 and claudin-5 (tight junctions) was detected in early and mid-gestation-derived hfBECs, which also formed capillary-like tube structures, confirming their BEC phenotype. P-gp and BCRP immunostaining was detected in capillary-like tubes and in the cytoplasm and nucleus of hfBECs. P-gp protein levels in the plasma membrane and nuclear protein fractions, as well as P-gp protein/ABCB1 mRNA and BCRP protein levels decreased (p < 0.05) in hfBECs, from early to mid-gestation. No differences in P-gp or BCRP activity in hfBECs were observed between the two age groups. The hfBECs from early and mid-gestation express functionally competent P-gp and BCRP drug transporters and may thus contribute to the BBB protective phenotype in the conceptus from early stages of pregnancy.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics ; ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism ; ATP-Binding Cassette Transporters/metabolism ; Brain/metabolism ; Drug Resistance, Multiple ; Endothelial Cells/metabolism ; Female ; Humans ; Neoplasm Proteins/metabolism ; Pregnancy
Chemical Substances	ABCB1 protein, human ; ABCG2 protein, human ; ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; ATP Binding Cassette Transporter, Subfamily G, Member 2 ; ATP-Binding Cassette Transporters ; Neoplasm Proteins
Language	English
Publishing date	2022-07-21
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11142259
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Article ; Online: Expression of severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across gestation and at the maternal-fetal interface in pregnancies complicated by preterm birth or preeclampsia.

Bloise, Enrrico / Zhang, Jianhong / Nakpu, Jittanan / Hamada, Hirotaka / Dunk, Caroline E / Li, Siliang / Imperio, Guinever E / Nadeem, Lubna / Kibschull, Mark / Lye, Phetcharawan / Matthews, Stephen G / Lye, Stephen J

American journal of obstetrics and gynecology

2020 Volume 224, Issue 3, Page(s) 298.e1–298.e8

Abstract: Background: Although there is some evidence that severe acute respiratory syndrome coronavirus 2 can invade the human placenta, limited data exist on the gestational age-dependent expression profile of the severe acute respiratory syndrome coronavirus 2 ...

Abstract	Background: Although there is some evidence that severe acute respiratory syndrome coronavirus 2 can invade the human placenta, limited data exist on the gestational age-dependent expression profile of the severe acute respiratory syndrome coronavirus 2 cell entry mediators, angiotensin-converting enzyme 2 and transmembrane protease serine 2, at the human maternal-fetal interface. There is also no information as to whether the expression of these mediators is altered in pregnancies complicated by preeclampsia or preterm birth. This is important because the expression of decidual and placental angiotensin-converting enzyme 2 and transmembrane protease serine 2 across gestation may affect the susceptibility of pregnancies to vertical transmission of severe acute respiratory syndrome coronavirus 2. Objective: This study aimed to investigate the expression pattern of specific severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across human pregnancy and in paired samples of decidua and placenta in pregnancies complicated by preterm birth or preeclampsia compared with those in term uncomplicated pregnancies. Study design: In this study, 2 separate cohorts of patients, totaling 87 pregnancies, were included. The first cohort was composed of placentae from first- (7-9 weeks), second- (16-18 weeks), and third-trimester preterm (26-31 weeks) and third-trimester term (38-41 weeks) pregnancies (n=5/group), whereas the second independent cohort included matched decidua and placentae from pregnancies from term uncomplicated pregnancies (37-41 weeks' gestation; n=14) and pregnancies complicated by preterm birth (26-37 weeks' gestation; n=11) or preeclampsia (25-37 weeks' gestation; n=42). Samples were subjected to quantitative polymerase chain reaction and next-generation sequencing or RNA sequencing for next-generation RNA sequencing for angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA expression quantification, respectively. Results: In the first cohort, angiotensin-converting enzyme 2 and transmembrane protease serine 2, exhibited a gestational age-dependent expression profile, that is, angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA was higher (P<.05) in the first-trimester placenta than in second-trimester, preterm birth, and term placentae (P<.05) and exhibited a negative correlation with gestational age (P<.05). In the second cohort, RNA sequencing demonstrated very low or undetectable expression levels of angiotensin-converting enzyme 2 in preterm birth, preeclampsia, and term decidua and in placentae from late gestation. In contrast, transmembrane protease serine 2 was expressed in both decidual and placental samples but did not change in pregnancies complicated by either preterm birth or preeclampsia. Conclusion: The increased expression of these severe acute respiratory syndrome coronavirus 2 cell entry-associated genes in the placenta in the first trimester of pregnancy compared with those in later stages of pregnancy suggests the possibility of differential susceptibility to placental entry to severe acute respiratory syndrome coronavirus 2 across pregnancy. Even though there is some evidence of increased rates of preterm birth associated with severe acute respiratory syndrome coronavirus 2 infection, we found no increase in mRNA expression of angiotensin-converting enzyme 2 or transmembrane protease serine 2 at the maternal-fetal interface.
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; COVID-19/etiology ; Female ; Humans ; Placenta/metabolism ; Placenta/virology ; Pre-Eclampsia/metabolism ; Pregnancy ; Premature Birth/metabolism ; RNA, Messenger/analysis ; SARS-CoV-2/physiology ; Serine Endopeptidases/genetics ; Virus Internalization
Chemical Substances	RNA, Messenger ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Keywords	covid19
Language	English
Publishing date	2020-08-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2020.08.055
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Article ; Online: Function of Multidrug Resistance Transporters is Disrupted by Infection Mimics in Human Brain Endothelial Cells.

Eustaquio Do Imperio, Guinever / Lye, Phetcharawan / Bloise, Enrrico / Matthews, Stephen G

Tissue barriers

2021 Volume 9, Issue 2, Page(s) 1860616

Abstract: P-glycoprotein ( ...

Abstract	P-glycoprotein (
MeSH term(s)	Biological Transport/physiology ; Brain/metabolism ; Drug Resistance, Multiple/drug effects ; Endothelial Cells/metabolism ; Gene Expression/genetics ; Humans
Language	English
Publishing date	2021-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2168-8370
ISSN (online)	2168-8370
DOI	10.1080/21688370.2020.1860616
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Article ; Online: Gestational age-dependent gene expression profiling of ATP-binding cassette transporters in the healthy human placenta.

Imperio, Guinever E / Javam, Mohsen / Lye, Phetcharawan / Constantinof, Andrea / Dunk, Caroline E / Reis, Fernando M / Lye, Stephen J / Gibb, William / Matthews, Stephen G / Ortiga-Carvalho, Tania Maria / Bloise, Enrrico

Journal of cellular and molecular medicine

2018 Volume 23, Issue 1, Page(s) 610–618

Abstract: The ATP-binding cassette (ABC) transporters control placental transfer of several nutrients, steroids, immunological factors, chemicals, and drugs at the maternal-fetal interface. We and others have demonstrated a gestational age-dependent expression ... ...

Abstract	The ATP-binding cassette (ABC) transporters control placental transfer of several nutrients, steroids, immunological factors, chemicals, and drugs at the maternal-fetal interface. We and others have demonstrated a gestational age-dependent expression pattern of two ABC transporters, P-glycoprotein and breast cancer resistance protein throughout pregnancy. However, no reports have comprehensively elucidated the expression pattern of all 50 ABC proteins, comparing first trimester and term human placentae. We hypothesized that placental ABC transporters are expressed in a gestational-age dependent manner in normal human pregnancy. Using the TaqMan
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics ; ATP-Binding Cassette Transporters/genetics ; Adult ; Female ; Gene Expression Profiling/methods ; Gestational Age ; Humans ; Neoplasm Proteins/genetics ; Placenta/metabolism ; Pregnancy ; Transcriptome/genetics ; Trophoblasts/metabolism
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; ATP-Binding Cassette Transporters ; Neoplasm Proteins
Language	English
Publishing date	2018-11-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2074559-X
ISSN	1582-4934 ; 1582-4934 ; 1582-1838
ISSN (online)	1582-4934
ISSN	1582-4934 ; 1582-1838
DOI	10.1111/jcmm.13966
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Article: Expression of severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across gestation and at the maternal-fetal interface in pregnancies complicated by preterm birth or preeclampsia

Am. j. obstet. gynecol

Abstract: BACKGROUND: Although there is some evidence that severe acute respiratory syndrome coronavirus 2 can invade the human placenta, limited data exist on the gestational age-dependent expression profile of the severe acute respiratory syndrome coronavirus 2 ... ...

Abstract	BACKGROUND: Although there is some evidence that severe acute respiratory syndrome coronavirus 2 can invade the human placenta, limited data exist on the gestational age-dependent expression profile of the severe acute respiratory syndrome coronavirus 2 cell entry mediators, angiotensin-converting enzyme 2 and transmembrane protease serine 2, at the human maternal-fetal interface. There is also no information as to whether the expression of these mediators is altered in pregnancies complicated by preeclampsia or preterm birth. This is important because the expression of decidual and placental angiotensin-converting enzyme 2 and transmembrane protease serine 2 across gestation may affect the susceptibility of pregnancies to vertical transmission of severe acute respiratory syndrome coronavirus 2. OBJECTIVE: This study aimed to investigate the expression pattern of specific severe acute respiratory syndrome coronavirus 2 cell entry genes, angiotensin-converting enzyme 2 and transmembrane protease serine 2, in the placenta across human pregnancy and in paired samples of decidua and placenta in pregnancies complicated by preterm birth or preeclampsia compared with those in term uncomplicated pregnancies. STUDY DESIGN: In this study, 2 separate cohorts of patients, totaling 87 pregnancies, were included. The first cohort was composed of placentae from first- (7-9 weeks), second- (16-18 weeks), and third-trimester preterm (26-31 weeks) and third-trimester term (38-41 weeks) pregnancies (n=5/group), whereas the second independent cohort included matched decidua and placentae from pregnancies from term uncomplicated pregnancies (37-41 weeks' gestation; n=14) and pregnancies complicated by preterm birth (26-37 weeks' gestation; n=11) or preeclampsia (25-37 weeks' gestation; n=42). Samples were subjected to quantitative polymerase chain reaction and next-generation sequencing or RNA sequencing for next-generation RNA sequencing for angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA expression quantification, respectively. RESULTS: In the first cohort, angiotensin-converting enzyme 2 and transmembrane protease serine 2, exhibited a gestational age-dependent expression profile, that is, angiotensin-converting enzyme 2 and transmembrane protease serine 2 mRNA was higher (P<.05) in the first-trimester placenta than in second-trimester, preterm birth, and term placentae (P<.05) and exhibited a negative correlation with gestational age (P<.05). In the second cohort, RNA sequencing demonstrated very low or undetectable expression levels of angiotensin-converting enzyme 2 in preterm birth, preeclampsia, and term decidua and in placentae from late gestation. In contrast, transmembrane protease serine 2 was expressed in both decidual and placental samples but did not change in pregnancies complicated by either preterm birth or preeclampsia. CONCLUSION: The increased expression of these severe acute respiratory syndrome coronavirus 2 cell entry-associated genes in the placenta in the first trimester of pregnancy compared with those in later stages of pregnancy suggests the possibility of differential susceptibility to placental entry to severe acute respiratory syndrome coronavirus 2 across pregnancy. Even though there is some evidence of increased rates of preterm birth associated with severe acute respiratory syndrome coronavirus 2 infection, we found no increase in mRNA expression of angiotensin-converting enzyme 2 or transmembrane protease serine 2 at the maternal-fetal interface.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #773900
Database	COVID19

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Article ; Online: Hypoxia alters the expression of ACE2 and TMPRSS2 SARS-CoV-2 cell entry mediators in hCMEC/D3 brain endothelial cells.

Imperio, Guinever E / Lye, Phetcharawan / Mughis, Hafsah / Hamada, Hirotaka / Bloise, Enrrico / Lye, Stephen J / Matthews, Stephen G

Microvascular research

2021 Volume 138, Page(s) 104232

Abstract: The mechanisms by which the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induces neurological complications remain to be elucidated. We aimed to identify possible effects of hypoxia on the expression of SARS-CoV-2 cell entry mediators, ... ...

Abstract	The mechanisms by which the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induces neurological complications remain to be elucidated. We aimed to identify possible effects of hypoxia on the expression of SARS-CoV-2 cell entry mediators, angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) protein, in human brain endothelial cells, in vitro. hCMEC/D3 cells were exposed to different oxygen tensions: 20% (Control group), 8% or 2% O
MeSH term(s)	Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; Brain/blood supply ; COVID-19/enzymology ; COVID-19/virology ; Cell Hypoxia ; Cell Line ; Endothelial Cells/enzymology ; Endothelial Cells/virology ; Gene Expression Regulation ; Host-Pathogen Interactions ; Humans ; SARS-CoV-2/pathogenicity ; Serine Endopeptidases/genetics ; Serine Endopeptidases/metabolism ; Virus Internalization
Chemical Substances	ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Serine Endopeptidases (EC 3.4.21.-) ; TMPRSS2 protein, human (EC 3.4.21.-)
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80307-8
ISSN	1095-9319 ; 0026-2862
ISSN (online)	1095-9319
ISSN	0026-2862
DOI	10.1016/j.mvr.2021.104232
Database	MEDical Literature Analysis and Retrieval System OnLINE

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