Glycogen metabolism in rat heart muscle cultures after hypoxia

Ayelet Vigoda, Liaman K. Mamedova, Vladimir Shneyvays, Abram Katz, Asher Shainberg

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22 Scopus citations

Abstract

Elevated glycogen levels in heart have been shown to have cardioprotective effects against ischemic injury. We have therefore established a model for elevating glycogen content in primary rat cardiac cells grown in culture and examined potential mechanisms for the elevation (glycogen supercompensation). Glycogen was depleted by exposing the cells to hypoxia for 2 h in the absence of glucose in the medium. This was followed by incubating the cells with 28 mM glucose in normoxia for up to 120 h. Hypoxia decreased glycogen content to about 15% of control, oxygenated cells. This was followed by a continuous increase in glycogen in the hypoxia treated cells during the 120 h recovery period in normoxia. By 48 h after termination of hypoxia, the glycogen content had returned to baseline levels and by 120 h glycogen was about 150% of control. The increase in glycogen at 120 h was associated with comparable relative increases in glucose uptake (∼ 180% of control) and the protein level of the glut-1 transporter (∼ 170% of control), whereas the protein level of the glut-4 transporter was decreased to < 10% of control. By 120 h, the hypoxia-treated cells also exhibited marked increases in the total (∼ 170% of control) and fractional activity of glycogen synthase (control, ∼ 15%; hypoxia-treated, ∼ 30%). Concomitantly, the hypoxia-treated cells also exhibited marked decreases in the total (∼ 50% of control) and fractional activity of glycogen phosphorylase (control, ∼ 50%; hypoxia-treated, ∼ 25%). Thus, we have established a model of glycogen supercompensation in cultures of cardiac cells that is explained by concerted increases in glucose uptake and glycogen synthase activity and decreases in phosphorylase activity. This model should prove useful in studying the cardioprotective effects of glycogen.

Original languageEnglish
Pages (from-to)311-318
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume254
Issue number1-2
DOIs
StatePublished - Dec 2003

Bibliographical note

Funding Information:
We thank A. Isaac and T. Zinman for their valuable technical assistance and S. Victor for preparing the manuscript. This research was supported by grants from the Israel Science Foundation (Grant No. 373/98-18.1) (AS) and the Swedish National Center for Sports (AK).

Funding

We thank A. Isaac and T. Zinman for their valuable technical assistance and S. Victor for preparing the manuscript. This research was supported by grants from the Israel Science Foundation (Grant No. 373/98-18.1) (AS) and the Swedish National Center for Sports (AK).

FundersFunder number
Swedish National Center for Sports
Israel Science Foundation373/98-18.1

    Keywords

    • Glut-1
    • Glut-4
    • Glycogen phosphorylase
    • Glycogen synthase

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