期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 290, 期 1, 页码 C57-C65出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00263.2005
关键词
hypertrophy; left ventricle; calcium channels; calcium signaling
资金
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R29HL048789, R01HL067464, R01HL048789] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK055647] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL-67464, HL-076165, HL-48789] Funding Source: Medline
- NIDDK NIH HHS [DK-55647] Funding Source: Medline
We previously reported that glucosamineand hyperglycemia attenuate the response of to inositol 1,4,5-trisphosphate-generating agonists such as ANG II. This appears to be related to an increase in flux through the hexosamine biosynthesis pathway (HBP) and decreased Ca2+ entry into the cells; however, a direct link between HBP and intracellular Ca2+ homeostasis has not been established. Therefore, using neonatal rat ventricular myocytes, we investigated the relationship between glucosamine treatment; the concentration of UDP-N-acetylglucosamine (UDP-GlcNAc), an end product of the HBP; and the level of protein O-linked N-acetylglucosamine (O-GlcNAc) on ANG II-mediated changes in intracellular free Ca2+ concentration ([Ca2+](i)). We found that glucosamine blocked ANG II-induced [Ca2+](i) increase and that this phenomenon was associated with a significant increase in UDP-GlcNAc and O-GlcNAc levels. O-(2-acetamido-2-deoxy-(D)-glucopyranosylidene)amino-N-phenylcarbamate, an inhibitor of O-GlcNAcase that increased O- GlcNAc levels without changing UDPGlcNAc concentrations, mimicked the effect of glucosamine on the ANG II-induced increase in [Ca2+](i). An inhibitor of O-GlcNAc-transferase, alloxan, prevented the glucosamine-induced increase in O- GlcNAc but not the increase in UDP-GlcNAc; however, alloxan abrogated the inhibition of the ANG II-induced increase in [Ca2+](i). These data support the notion that changes in O- GlcNAc levels mediated via increased HBP flux may be involved in the regulation of [Ca2+](i) homeostasis in the heart.
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