Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2

Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing c...

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Published in:Genetics and Molecular Research
Main Author: Hanafi N.I.; Mohamed A.S.; Md Noor J.; Abdul Hamid Hasani N.; Siran R.; Osman N.J.; Ab Rahim S.; Sheikh Abdul Kadir S.H.
Format: Article
Language:English
Published: Fundacao de Pesquisas Cientificas de Ribeirao Preto 2016
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85011771016&doi=10.4238%2fgmr.15028150&partnerID=40&md5=b7f8089ab48055aece2c84d849640044
id 2-s2.0-85011771016
spelling 2-s2.0-85011771016
Hanafi N.I.; Mohamed A.S.; Md Noor J.; Abdul Hamid Hasani N.; Siran R.; Osman N.J.; Ab Rahim S.; Sheikh Abdul Kadir S.H.
Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2
2016
Genetics and Molecular Research
15
2
10.4238/gmr.15028150
https://www.scopus.com/inward/record.uri?eid=2-s2.0-85011771016&doi=10.4238%2fgmr.15028150&partnerID=40&md5=b7f8089ab48055aece2c84d849640044
Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA regulates activation of ERK and Akt survival signaling pathways and SMases in protecting cardiac cells against hypoxia. Neonatal cardiomyocytes were isolated from 0- to 2-day-old Sprague Dawley rats, and given 100 μM CoCl2, 150 μM H2O2, or placed in a hypoxia chamber for 24 h. The ameliorative effects of 100-μM UDCA treatment for 12 h were then assessed using MTS, QuantiGene Plex (for Smpd1 and Smpd2), and SMase assays, beating rate assessment, and western blotting (for ERK and Akt). Data were analyzed by the paired Student t-tests and one-way analyses of variance. Cell viability decreased significantly after H2O2 (85%), CoCl2 (50%), and hypoxia chamber (52%) treatments compared to the untreated control (100%). UDCA significantly counteracted the effects of chamber- and CoCl2- induced hypoxia on viability and beating rate. However, no significant differences were observed in acid SMase gene and protein expression between the untreated, CoCl2, and UDCA-CoCl2 groups. In contrast, neutral SMase gene and protein expression did significantly differ between the latter two groups. ERK and Akt phosphorylation was higher in hypoxic cardiomyocytes treated with UDCA than those given CoCl2 alone. In conclusion, UDCA regulates the activation of survival signaling proteins and SMases in neonatal rat cardiomyocytes during hypoxia. © FUNPEC-RP.
Fundacao de Pesquisas Cientificas de Ribeirao Preto
16765680
English
Article
All Open Access; Bronze Open Access
author Hanafi N.I.; Mohamed A.S.; Md Noor J.; Abdul Hamid Hasani N.; Siran R.; Osman N.J.; Ab Rahim S.; Sheikh Abdul Kadir S.H.
spellingShingle Hanafi N.I.; Mohamed A.S.; Md Noor J.; Abdul Hamid Hasani N.; Siran R.; Osman N.J.; Ab Rahim S.; Sheikh Abdul Kadir S.H.
Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2
author_facet Hanafi N.I.; Mohamed A.S.; Md Noor J.; Abdul Hamid Hasani N.; Siran R.; Osman N.J.; Ab Rahim S.; Sheikh Abdul Kadir S.H.
author_sort Hanafi N.I.; Mohamed A.S.; Md Noor J.; Abdul Hamid Hasani N.; Siran R.; Osman N.J.; Ab Rahim S.; Sheikh Abdul Kadir S.H.
title Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2
title_short Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2
title_full Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2
title_fullStr Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2
title_full_unstemmed Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2
title_sort Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2
publishDate 2016
container_title Genetics and Molecular Research
container_volume 15
container_issue 2
doi_str_mv 10.4238/gmr.15028150
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-85011771016&doi=10.4238%2fgmr.15028150&partnerID=40&md5=b7f8089ab48055aece2c84d849640044
description Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA regulates activation of ERK and Akt survival signaling pathways and SMases in protecting cardiac cells against hypoxia. Neonatal cardiomyocytes were isolated from 0- to 2-day-old Sprague Dawley rats, and given 100 μM CoCl2, 150 μM H2O2, or placed in a hypoxia chamber for 24 h. The ameliorative effects of 100-μM UDCA treatment for 12 h were then assessed using MTS, QuantiGene Plex (for Smpd1 and Smpd2), and SMase assays, beating rate assessment, and western blotting (for ERK and Akt). Data were analyzed by the paired Student t-tests and one-way analyses of variance. Cell viability decreased significantly after H2O2 (85%), CoCl2 (50%), and hypoxia chamber (52%) treatments compared to the untreated control (100%). UDCA significantly counteracted the effects of chamber- and CoCl2- induced hypoxia on viability and beating rate. However, no significant differences were observed in acid SMase gene and protein expression between the untreated, CoCl2, and UDCA-CoCl2 groups. In contrast, neutral SMase gene and protein expression did significantly differ between the latter two groups. ERK and Akt phosphorylation was higher in hypoxic cardiomyocytes treated with UDCA than those given CoCl2 alone. In conclusion, UDCA regulates the activation of survival signaling proteins and SMases in neonatal rat cardiomyocytes during hypoxia. © FUNPEC-RP.
publisher Fundacao de Pesquisas Cientificas de Ribeirao Preto
issn 16765680
language English
format Article
accesstype All Open Access; Bronze Open Access
record_format scopus
collection Scopus
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