HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Buy All Versions of this Article: fj.08-121772v1 23/4/1072    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Föller, M. Articles by Lang, F. Search for Related Content PubMed PubMed Citation Articles by Föller, M. Articles by Lang, F.

Regulation of erythrocyte survival by AMP-activated protein kinase

Michael Föller^*, Mentor Sopjani^*, Saisudha Koka^*, Shuchen Gu^*, Hasan Mahmud^*, Kan Wang^*, Elisa Floride^*, Erwin Schleicher, Eberhard Schulz, Thomas Münzel and Florian Lang^*

^* Department of Physiology and

Department of Endocrinology, Diabetes, Vascular Medicine, Nephrology, and Clinical Chemistry, University of Tübingen, Tübingen, Germany; and

Department of Cardiology, University of Mainz, Mainz, Germany

¹Correspondence: Physiologisches Institut, der Universität Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany. E-mail: florian.lang{at}uni-tuebingen.de

AMP-activated protein kinase (AMPK), an energy-sensing enzyme, counteracts energy depletion by stimulation of energy production and limitation of energy utilization. On energy depletion, erythrocytes undergo suicidal death or eryptosis, triggered by an increase in cytosolic Ca²⁺ activity ([Ca²⁺]_i) and characterized by cell shrinkage and phosphatidylserine (PS) exposure at the erythrocyte surface. The present study explored whether AMPK participates in the regulation of eryptosis. Western blotting and confocal microscopy disclosed AMPK expression in erythrocytes. [Ca²⁺]_i (Fluo3 fluorescence), cell volume (forward scatter), and PS exposure (annexin V binding) were determined by fluorescence-activated cell sorting (FACS) analysis. Glucose removal increased [Ca²⁺]_i, decreased cell volume, and increased PS exposure. The AMPK-inhibitor compound C (20 µM) did not significantly modify eryptosis under glucose-replete conditions but significantly augmented the eryptotic effect of glucose withdrawal. An increase in [Ca²⁺]_i by Ca²⁺ ionophore ionomycin triggered eryptosis, an effect blunted by the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR; 1 mM). As compared with erythrocytes from wild-type littermates (ampk^+/+), erythrocytes from AMPK1-deficient mice (ampk^–/–) were significantly more susceptible to the eryptotic effect of energy depletion. The ampk^–/– mice were anemic despite excessive reticulocytosis, and they suffered from severe splenomegaly, again pointing to enhanced erythrocyte turnover. The observations disclose a critical role of AMPK in the survival of circulating erythrocytes.—Föller, M., Sopjani, M., Koka, S., Gu, S., Mahmud, H., Wang, K., Floride, E., Schleicher, E., Schulz, E., Münzel, T., Lang, F. Regulation of erythrocyte survival by AMP-activated protein kinase.

Key Words: cell volume • annexin • eryptosis • calcium • phosphatidylserine