caa a22 4500 606237070 CHVBK 20210128101251.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s11010-014-2292-z doi (NATIONALLICENCE)springer-10.1007/s11010-014-2292-z Modulation of apoptosis by sulforaphane is associated with PGC-1α stimulation and decreased oxidative stress in cardiac myoblasts [Elektronische Daten] [Rafael Fernandes, Jéssica Bonetto, Boran Baregzay, Alexandre de Castro, Stephanie Puukila, Heidi Forsyth, Paulo Schenkel, Susana Llesuy, Ilma Brum, Alex Araujo, Neelam Khaper, Adriane Belló-Klein] Sulforaphane is a naturally occurring isothiocyanate capable of stimulating cellular antioxidant defenses and inducing phase 2 detoxifying enzymes, which can protect cells against oxidative damage. Oxidative stress and apoptosis are intimately involved in the pathophysiology of cardiac diseases. Although sulforaphane is known for its anticancer benefits, its role in cardiac cells is just emerging. The aim of the present study was to investigate whether sulforaphane can modulate oxidative stress, apoptosis, and correlate with PGC-1α, a transcriptional cofactor involved in energy metabolism. H9c2 cardiac myoblasts were incubated with R-sulforaphane 5µmol/L for 24h. Cell viability, ANP gene expression, oxidative stress and apoptosis markers, and protein expression of PGC-1α were studied. In cells treated with sulforaphane, cellular viability increased (12%) and ANP gene expression decreased (46%) compared to control cells. Moreover, sulforaphane induced a significant increase in superoxide dismutase (103%), catalase (101%), and glutathione S-transferase (72%) activity, reduced reactive oxygen species levels (15%) and lipid peroxidation (65%), as well as stimulated the expression of the cytoprotective enzyme heme oxygenase-1 (4-fold). Sulforaphane also promoted an increase in the expression of the anti-apoptotic protein Bcl-2 (60%), decreasing the Bax/Bcl-2 ratio. Active Caspase 3\7 and p-JNK/JNK were also reduced by sulforaphane, suggesting a reduction in apoptotic signaling. This was associated with an increased protein expression of PGC-1α (42%). These results suggest that sulforaphane offers cytoprotection to cardiac cells by activating PGC1-α, reducing oxidative stress, and decreasing apoptosis signaling. Springer Science+Business Media New York, 2014 Oxidative stress nationallicence Heme oxygenase-1 nationallicence PGC-1 alpha nationallicence Bcl-2 nationallicence Caspase nationallicence Fernandes Rafael Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut Bonetto Jéssica Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut Baregzay Boran Department of Biology, Lakehead University, Thunder Bay, ON, Canada aut de Castro Alexandre Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut Puukila Stephanie Department of Biology, Lakehead University, Thunder Bay, ON, Canada aut Forsyth Heidi Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, ON, Canada aut Schenkel Paulo Department of Physiology, Federal University of Pelotas (UFPel), Pelotas, RS, Brazil aut Llesuy Susana General and Inorganic Chemistry Division, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina aut Brum Ilma Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut Araujo Alex Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut Khaper Neelam Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, ON, Canada aut Belló-Klein Adriane Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 61-70 0300-8177 401:1-2<61 2015 401 11010 https://doi.org/10.1007/s11010-014-2292-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2292-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fernandes Rafael Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Bonetto Jéssica Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Baregzay Boran Department of Biology, Lakehead University, Thunder Bay, ON, Canada aut NATIONALLICENCE 700 1- de Castro Alexandre Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Puukila Stephanie Department of Biology, Lakehead University, Thunder Bay, ON, Canada aut NATIONALLICENCE 700 1- Forsyth Heidi Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, ON, Canada aut NATIONALLICENCE 700 1- Schenkel Paulo Department of Physiology, Federal University of Pelotas (UFPel), Pelotas, RS, Brazil aut NATIONALLICENCE 700 1- Llesuy Susana General and Inorganic Chemistry Division, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina aut NATIONALLICENCE 700 1- Brum Ilma Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Araujo Alex Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut NATIONALLICENCE 700 1- Khaper Neelam Medical Sciences Division, Northern Ontario School of Medicine, Lakehead University, Thunder Bay, ON, Canada aut NATIONALLICENCE 700 1- Belló-Klein Adriane Laboratory of Cardiovascular Physiology, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 61-70 0300-8177 401:1-2<61 2015 401 11010