Open Access

AMPK activation protects astrocytes from hypoxia‑induced cell death

  • Authors:
    • Leli Barialai
    • Maja I. Strecker
    • Anna‑Luisa Luger
    • Manuel Jäger
    • Ines Bruns
    • Alina C.M. Sittig
    • Iris C. Mildenberger
    • Sonja M. Heller
    • Alberto Delaidelli
    • Nadja I. Lorenz
    • Martin Voss
    • Michael W. Ronellenfitsch
    • Joachim P. Steinbach
    • Michael C. Burger
  • View Affiliations

  • Published online on: March 5, 2020     https://doi.org/10.3892/ijmm.2020.4528
  • Pages: 1385-1396
  • Copyright: © Barialai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Adenosine monophosphate (AMP)‑activated protein kinase (AMPK) is a major cellular energy sensor that is activated by an increase in the AMP/adenosine triphosphate (ATP) ratio. This causes the initiation of adaptive cellular programs, leading to the inhibition of anabolic pathways and increasing ATP synthesis. AMPK indirectly inhibits mammalian target of rapamycin (mTOR) complex 1 (mTORC1), a serine/threonine kinase and central regulator of cell growth and metabolism, which integrates various growth inhibitory signals, such as the depletion of glucose, amino acids, ATP and oxygen. While neuroprotective approaches by definition focus on neurons, that are more sensitive under cell stress conditions, astrocytes play an important role in the cerebral energy homeostasis during ischemia. Therefore, the protection of astrocytic cells or other glial cells may contribute to the preservation of neuronal integrity and function. In the present study, it was thus hypothesized that a preventive induction of energy deprivation‑activated signaling pathways via AMPK may protect astrocytes from hypoxia and glucose deprivation. Hypoxia‑induced cell death was measured in a paradigm of hypoxia and partial glucose deprivation in vitro in the immortalized human astrocytic cell line SVG. Both the glycolysis inhibitor 2‑deoxy‑d‑glucose (2DG) and the AMPK activator A‑769662 induced the phosphorylation of AMPK, resulting in mTORC1 inhibition, as evidenced by a decrease in the phosphorylation of the target ribosomal protein S6 (RPS6). Treatment with both 2DG and A‑769662 also decreased glucose consumption and lactate production. Furthermore, A‑769662, but not 2DG induced an increase in oxygen consumption, possibly indicating a more efficient glucose utilization through oxidative phosphorylation. Hypoxia‑induced cell death was profoundly reduced by treatment with 2DG or A‑769662. On the whole, the findings of the present study demonstrate, that AMPK activation via 2DG or A‑769662 protects astrocytes under hypoxic and glucose‑depleted conditions.

Related Articles

Journal Cover

May 2020
Volume 45 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
APA
Barialai, L., Strecker, M.I., Luger, A., Jäger, M., Bruns, I., Sittig, A.C. ... Burger, M.C. (2020). AMPK activation protects astrocytes from hypoxia‑induced cell death. International Journal of Molecular Medicine, 45, 1385-1396. https://doi.org/10.3892/ijmm.2020.4528
MLA
Barialai, L., Strecker, M. I., Luger, A., Jäger, M., Bruns, I., Sittig, A. C., Mildenberger, I. C., Heller, S. M., Delaidelli, A., Lorenz, N. I., Voss, M., Ronellenfitsch, M. W., Steinbach, J. P., Burger, M. C."AMPK activation protects astrocytes from hypoxia‑induced cell death". International Journal of Molecular Medicine 45.5 (2020): 1385-1396.
Chicago
Barialai, L., Strecker, M. I., Luger, A., Jäger, M., Bruns, I., Sittig, A. C., Mildenberger, I. C., Heller, S. M., Delaidelli, A., Lorenz, N. I., Voss, M., Ronellenfitsch, M. W., Steinbach, J. P., Burger, M. C."AMPK activation protects astrocytes from hypoxia‑induced cell death". International Journal of Molecular Medicine 45, no. 5 (2020): 1385-1396. https://doi.org/10.3892/ijmm.2020.4528