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Gong J., Jing L.
Department of Anesthesiology, Zhongda Hospital and College of Medicine, Southeast University, Nanjing, Jiangsu, China
BACKGROUND: Glutamine (Gln) has been shown to induce heat shock protein (HSP) expression and to attenuate lipopolysaccharide (LPS)–mediated cardiovascular dysfunction, but the underlying mechanisms are not fully clear. We tested the hypothesis that protection by Gln-induced HSP70 expression is due to enhanced O-linked β-N-acetylglucosamine (O-GlcNAc) modification levels and subsequent increases in the levels of endonuclear heat shock protein factor-1 (HSF-1) expression and HSF-1 transcriptional activity in LPS-treated cardiomyocytes.
METHODS: Primary cultures of neonatal rat cardiomyocytes were divided into control, LPS (4 μg/mL), Gln+LPS (Gln 5 mM+LPS 4 μg/mL), Gln+LPS+Alloxan (an O-linked-N-acetyl glucosamine transferase inhibitor, 1 mM) and Gln+LPS+PUGNAc (an O-GlcNAcase inhibitor; 100 μM) groups. After incubation for six hours, the levels of cardiomyocyte viability, lactate dehydrogenase (LDH) activity, O-GlcNAc modification, endonuclear HSF-1 expression, HSF-1 transcription activity and cellular HSP70 expression were measured in all groups.
RESULTS: There were no significant differences in cell viability among the five groups. LDH activity levels were much higher in the LPS group than in the control group, but they markedly decreased in the Gln+LPS group (P<0.05). Gln’s protection in the Gln+LPS group was associated with a significant increase in the levels of O-GlcNAc modification, endonuclear HSF-1 expression, HSF-1 transcription activity and cellular HSP70 expression compared to the LPS group (P<0.05). The protective action by Gln in LPS-treated cardiomyocytes could either be mimicked by 1 μM PUGNAc or banished by 1 mM alloxan.
CONCLUSION: Gln induces HSP70 expression and attenuates LPS-induced cardiomyocyte damage. The molecular mechanism of Gln-induced HSP70 expression appears to be mediated via enhancement of O-GlcNAc modification and subsequently to increase levels of endonuclear HSF-1 expression and HSF-1 transcription activity.