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Glucosamine Protects Neonatal Cardiomyocytes from Ischemia‐Reperfusion Injury through Translocation of BCL2 Family Proteins
Author(s) -
Champattanachai Voraratt,
Marchase Richard B,
Chatham John C
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a866
Subject(s) - chromosomal translocation , apoptosis , cytochrome c , mitochondrion , glucosamine , chemistry , reperfusion injury , reactive oxygen species , ischemia , microbiology and biotechnology , biology , biochemistry , medicine , gene
We have previously reported that in neonatal rat ventricular myocytes (NRVMs) glucosamine (GlcN) treatment increased viability and decreased apoptosis following ischemia/reperfusion (I/R) and this was associated with increased levels of O‐linked N‐acetylglucosamine (O‐GlcNAc) on proteins. The specific mechanisms underlying this protection have not been identified; therefore, the goal of this study was to determine whether GlcN treatment altered mitochondrial translocation of the BCL2 family of proteins, which play a critical role in regulating mitochondrial‐mediated apoptosis. NRVMs were exposed to 4 hours ischemia and 2 hours of reperfusion±5mM GlcN. Consistent with earlier studies GlcN significantly increased O ‐GlcNAc levels and reduced both necrosis and apoptosis. In untreated cells, I/R increased translocation of both BCL2 and Bad to mitochondria; GlcN treatment increased mitochondrial O ‐GlcNAc levels, enhanced BCL2 and decreased Bad mitochondrial translocation and reduced cytochrome C release compared to the untreated cells. GlcN also delayed the loss of mitochondrial membrane potential following treatment of NRVMs with hydrogen peroxide (1mM). These data suggest that the protection of NRVMs associated with GlcN and increased O‐GlcNAc levels may be mediated by enhanced mitochondrial BCL2 translocation and attenuation of mitochondrial‐mediated apoptosis. (Supported by NIH grants R01 HL076165 and R01HL079364).