Labudović Borović, Milica

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  • Labudović Borović, Milica (1)
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Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies

Đokić, Vladimir; Gostimirović, Miloš; Rajković, Jovana; Rakočević, Jelena; Labudović-Borović, Milica; Janković, Svetlana; Stanišić, Jelena; Kostić, Milan; Đurić, Miloš; Gojković-Bukarica, Ljiljana

(2023)

TY  - JOUR
AU  - Đokić, Vladimir
AU  - Gostimirović, Miloš
AU  - Rajković, Jovana
AU  - Rakočević, Jelena
AU  - Labudović-Borović, Milica
AU  - Janković, Svetlana
AU  - Stanišić, Jelena
AU  - Kostić, Milan
AU  - Đurić, Miloš
AU  - Gojković-Bukarica, Ljiljana
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/11226
AB  - Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type cur-rents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collective-ly, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment.
AB  - Uvod/Cilj. Značajan niz dokaza ukazuje na to da su kanali Kv4.2 i Kv4.3 glavne komponente brzih prolazno- ispravljačkih struja kalijuma (struje tipa A). Pretpostavlja se da bi te struje mogle da budu uključene u održavanje membranskog potencijala ćelije, kao i u regulaciju propagacije i učestalosti akcionih potencijala. Međutim, vrlo malo se zna o prisustvu i funkciji struje tipa A u glatkim mišićima krvnih sudova čoveka, kao što je humana umbilikalna vena (HUV). S obzirom na njenu ključnu ulogu u adekvatnoj oksigenaciji fetusa, cilj rada bio je da se utvrdi da li su podtipovi kalijumovih kanala Kv4.2 i Kv4.3 prisutni u glatkim mišićima HUV-a i da se istraže potencijalne promene njihove ekspresije tokom patoloških stanja majke – gestacijskog dijabetesa melitusa (GDM) i arterijske hipertenzije (AH) izazvane trudnoćom (AHT). Metode. U istraživanje su uključene HUV sakupljene posle trudnoće zdravih porodilja, onih čije trudnoće su bile komplikovane GDM i AH. Svaka grupa sastojala se od 6 uzoraka HUV-a dobijenih iz 6 zdravih trudnoća, 6 trudnoća komplikovanih GDM i 6 trudnoća komplikovanih AH. Nakon farmakoloških analiza, urađene su imunohistohemijska (IH) analiza i Western blot. Rezultati. Primenom IH analize pokazan je sličan obrazac ekspresije obe podjedinice Kv4.2 i Kv4.3 kanala u glatkim mišićima HUV-a u svim grupama trudnica. Rezultati dobijeni Western blot-om bili su u skladu sa IH bojenjem. Ekspresija podjedinica Kv4.2 i Kv4.3 nije se značajno razlikovala između grupa trudnica. Zaključak. Ovo je prema našim saznanjima prva studija kojom je pokazano prisustvo Kv4.2 i Kv4.3 kalijumovih kanala u glatkim mišićima HUV-a zdravih porodilja, kao i onih porodilja čija je trudnoća bila praćena prisustvom GDM ili AHT. Ti kanali su najverovatnije glavne komponente brzih struja A-tipa, koji mogu biti relevantni za protok krvi majke i ploda i na taj način delovati protektivno za razvoj fetusa. Takođe, oni mogu predstavljati senzitivne pokazatelje hemodinamskih i/ili metaboličkih promena u lokalnoj fetomaternalnoj sredini.
T2  - Vojnosanitetski pregled
T1  - Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies
T1  - Ekspresija kalijumovih kanala Kv4.2 i Kv4.3 u humanim pupčanim venama zdravih trudnica, trudnica sa gestacijskim dijabetesom melitusom i trudnica sa gestacijskom hipertenzijom
VL  - 80
IS  - 1
SP  - 71
EP  - 77
DO  - 10.2298/VSP211014005D
ER  - 
@article{
author = "Đokić, Vladimir and Gostimirović, Miloš and Rajković, Jovana and Rakočević, Jelena and Labudović-Borović, Milica and Janković, Svetlana and Stanišić, Jelena and Kostić, Milan and Đurić, Miloš and Gojković-Bukarica, Ljiljana",
year = "2023",
abstract = "Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type cur-rents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collective-ly, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment., Uvod/Cilj. Značajan niz dokaza ukazuje na to da su kanali Kv4.2 i Kv4.3 glavne komponente brzih prolazno- ispravljačkih struja kalijuma (struje tipa A). Pretpostavlja se da bi te struje mogle da budu uključene u održavanje membranskog potencijala ćelije, kao i u regulaciju propagacije i učestalosti akcionih potencijala. Međutim, vrlo malo se zna o prisustvu i funkciji struje tipa A u glatkim mišićima krvnih sudova čoveka, kao što je humana umbilikalna vena (HUV). S obzirom na njenu ključnu ulogu u adekvatnoj oksigenaciji fetusa, cilj rada bio je da se utvrdi da li su podtipovi kalijumovih kanala Kv4.2 i Kv4.3 prisutni u glatkim mišićima HUV-a i da se istraže potencijalne promene njihove ekspresije tokom patoloških stanja majke – gestacijskog dijabetesa melitusa (GDM) i arterijske hipertenzije (AH) izazvane trudnoćom (AHT). Metode. U istraživanje su uključene HUV sakupljene posle trudnoće zdravih porodilja, onih čije trudnoće su bile komplikovane GDM i AH. Svaka grupa sastojala se od 6 uzoraka HUV-a dobijenih iz 6 zdravih trudnoća, 6 trudnoća komplikovanih GDM i 6 trudnoća komplikovanih AH. Nakon farmakoloških analiza, urađene su imunohistohemijska (IH) analiza i Western blot. Rezultati. Primenom IH analize pokazan je sličan obrazac ekspresije obe podjedinice Kv4.2 i Kv4.3 kanala u glatkim mišićima HUV-a u svim grupama trudnica. Rezultati dobijeni Western blot-om bili su u skladu sa IH bojenjem. Ekspresija podjedinica Kv4.2 i Kv4.3 nije se značajno razlikovala između grupa trudnica. Zaključak. Ovo je prema našim saznanjima prva studija kojom je pokazano prisustvo Kv4.2 i Kv4.3 kalijumovih kanala u glatkim mišićima HUV-a zdravih porodilja, kao i onih porodilja čija je trudnoća bila praćena prisustvom GDM ili AHT. Ti kanali su najverovatnije glavne komponente brzih struja A-tipa, koji mogu biti relevantni za protok krvi majke i ploda i na taj način delovati protektivno za razvoj fetusa. Takođe, oni mogu predstavljati senzitivne pokazatelje hemodinamskih i/ili metaboličkih promena u lokalnoj fetomaternalnoj sredini.",
journal = "Vojnosanitetski pregled",
title = "Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies, Ekspresija kalijumovih kanala Kv4.2 i Kv4.3 u humanim pupčanim venama zdravih trudnica, trudnica sa gestacijskim dijabetesom melitusom i trudnica sa gestacijskom hipertenzijom",
volume = "80",
number = "1",
pages = "71-77",
doi = "10.2298/VSP211014005D"
}
Đokić, V., Gostimirović, M., Rajković, J., Rakočević, J., Labudović-Borović, M., Janković, S., Stanišić, J., Kostić, M., Đurić, M.,& Gojković-Bukarica, L.. (2023). Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies. in Vojnosanitetski pregled, 80(1), 71-77.
https://doi.org/10.2298/VSP211014005D
Đokić V, Gostimirović M, Rajković J, Rakočević J, Labudović-Borović M, Janković S, Stanišić J, Kostić M, Đurić M, Gojković-Bukarica L. Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies. in Vojnosanitetski pregled. 2023;80(1):71-77.
doi:10.2298/VSP211014005D .
Đokić, Vladimir, Gostimirović, Miloš, Rajković, Jovana, Rakočević, Jelena, Labudović-Borović, Milica, Janković, Svetlana, Stanišić, Jelena, Kostić, Milan, Đurić, Miloš, Gojković-Bukarica, Ljiljana, "Expression of Kv4.2 and Kv4.3 potassium channels in human umbilical veins from normal, diabetic and hypertensive pregnancies" in Vojnosanitetski pregled, 80, no. 1 (2023):71-77,
https://doi.org/10.2298/VSP211014005D . .
1
1

Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity

Seke, Mariana; Petrović, Danijela; Labudović Borović, Milica; Jović, Danica; Borišev, Ivana; Kanački, Zdenko; Žikić, Dragan; Đorđević, Aleksandar

(Belgrade : University of Belgrade, Faculty of Biology, 2017)

TY  - CONF
AU  - Seke, Mariana
AU  - Petrović, Danijela
AU  - Labudović Borović, Milica
AU  - Jović, Danica
AU  - Borišev, Ivana
AU  - Kanački, Zdenko
AU  - Žikić, Dragan
AU  - Đorđević, Aleksandar
PY  - 2017
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12680
AB  - Introduction: Doxorubicin is the most prominent chemotherapeutic, but its clinical use is limited by its severe systemic toxicity. An iron overload aggravates anthracycline toxicity. Fullerenol in aqueous solutions is in the form of polyanionic nanoparticles, serving as a good carrier of positively charged ions, such as Fe2+. Fullerenol’s antioxidant activity has already been proved in different biological systems. The aim of our study was to investigate the effects of the fullerenol/iron nanocomposite on the rat liver as a pretreatment to doxorubicin application. Methods: After the 24h-treatment, adult male Wistar rats were sacrificed and livers were collected for ultrastructural and qRT-PCR analysis. Considering the ability of doxorubicin to induce oxidative stress, and the fullerenol’s capability to mitigate it, gene expression of enzymes involved in antioxidant defense was measured. Results: Ultrastructural analysis revealed that liver tissue was mainly preserved after the nanocomposite was applied prior to doxorubicin. However, the hepatocytes of animals treated with doxorubicin, presented significantly damaged morphology. Apoptosis of hepatocytes and endothelial cells, mitochondria of irregular size and with disruption of cristae, diffuse injury of capillaries were observed. RT-PCR results have shown that treatment with doxorubicin alone significantly increase the mRNA levels of catalase (p=0.008) and superoxide-dismutase (p=0.000003), while the pretreatment with the nanocomposite prior the doxirubicine treatment, dramaticly downregulated the mRNA levels of catalase (p=0.0004) and superoxide-dismutase (p=0.0001). Conclusion: Our results suggest that the fullerenol/iron nanocomposite applied as pretreatment to doxorubicin, demonstrated protection to the liver tissue and induced less damage to the hepatocytes in comparison to doxorubicin alone.
PB  - Belgrade : University of Belgrade, Faculty of Biology
C3  - CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts
T1  - Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity
SP  - 71
EP  - 71
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12680
ER  - 
@conference{
author = "Seke, Mariana and Petrović, Danijela and Labudović Borović, Milica and Jović, Danica and Borišev, Ivana and Kanački, Zdenko and Žikić, Dragan and Đorđević, Aleksandar",
year = "2017",
abstract = "Introduction: Doxorubicin is the most prominent chemotherapeutic, but its clinical use is limited by its severe systemic toxicity. An iron overload aggravates anthracycline toxicity. Fullerenol in aqueous solutions is in the form of polyanionic nanoparticles, serving as a good carrier of positively charged ions, such as Fe2+. Fullerenol’s antioxidant activity has already been proved in different biological systems. The aim of our study was to investigate the effects of the fullerenol/iron nanocomposite on the rat liver as a pretreatment to doxorubicin application. Methods: After the 24h-treatment, adult male Wistar rats were sacrificed and livers were collected for ultrastructural and qRT-PCR analysis. Considering the ability of doxorubicin to induce oxidative stress, and the fullerenol’s capability to mitigate it, gene expression of enzymes involved in antioxidant defense was measured. Results: Ultrastructural analysis revealed that liver tissue was mainly preserved after the nanocomposite was applied prior to doxorubicin. However, the hepatocytes of animals treated with doxorubicin, presented significantly damaged morphology. Apoptosis of hepatocytes and endothelial cells, mitochondria of irregular size and with disruption of cristae, diffuse injury of capillaries were observed. RT-PCR results have shown that treatment with doxorubicin alone significantly increase the mRNA levels of catalase (p=0.008) and superoxide-dismutase (p=0.000003), while the pretreatment with the nanocomposite prior the doxirubicine treatment, dramaticly downregulated the mRNA levels of catalase (p=0.0004) and superoxide-dismutase (p=0.0001). Conclusion: Our results suggest that the fullerenol/iron nanocomposite applied as pretreatment to doxorubicin, demonstrated protection to the liver tissue and induced less damage to the hepatocytes in comparison to doxorubicin alone.",
publisher = "Belgrade : University of Belgrade, Faculty of Biology",
journal = "CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts",
title = "Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity",
pages = "71-71",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12680"
}
Seke, M., Petrović, D., Labudović Borović, M., Jović, D., Borišev, I., Kanački, Z., Žikić, D.,& Đorđević, A.. (2017). Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity. in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts
Belgrade : University of Belgrade, Faculty of Biology., 71-71.
https://hdl.handle.net/21.15107/rcub_vinar_12680
Seke M, Petrović D, Labudović Borović M, Jović D, Borišev I, Kanački Z, Žikić D, Đorđević A. Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity. in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts. 2017;:71-71.
https://hdl.handle.net/21.15107/rcub_vinar_12680 .
Seke, Mariana, Petrović, Danijela, Labudović Borović, Milica, Jović, Danica, Borišev, Ivana, Kanački, Zdenko, Žikić, Dragan, Đorđević, Aleksandar, "Fullerenol/iron nanocomposite modulates doxorubicin-induced hepatotoxicity" in CoMBoS1 - 1st Congress of Molecular Biologists of Serbia with international participation : Book of abstracts (2017):71-71,
https://hdl.handle.net/21.15107/rcub_vinar_12680 .