Universität zu Köln

Schubert, Kai Michael, Qiu, Jiehua, Blodow, Stephanie, Wiedenmann, Margarethe, Lubomirov, Lubomir T., Pfitzer, Gabriele, Pohl, Ulrich and Schneider, Holger ORCID: 0000-0003-1556-0951 (2017). The AMP-Related Kinase (AMPK) Induces Ca2+-Independent Dilation of Resistance Arteries by Interfering With Actin Filament Formation. Circ.Res., 121 (2). S. 149 - 184. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1524-4571

Full text not available from this repository.

Abstract

Rationale: Decreasing Ca2+ sensitivity of vascular smooth muscle (VSM) allows for vasodilation without lowering of cytosolic Ca2+. This may be particularly important in states requiring maintained dilation, such as hypoxia. AMP-related kinase (AMPK) is an important cellular energy sensor in VSM. Regulation of Ca2+ sensitivity usually is attributed to myosin light chain phosphatase activity, but findings in non-VSM identified changes in the actin cytoskeleton. The potential role of AMPK in this setting is widely unknown. Objective: To assess the influence of AMPK on the actin cytoskeleton in VSM of resistance arteries with regard to potential Ca2+ desensitization of VSM contractile apparatus. Methods and Results: AMPK induced a slowly developing dilation at unchanged cytosolic Ca2+ levels in potassium chloride-constricted intact arteries isolated from mouse mesenteric tissue. This dilation was not associated with changes in phosphorylation of myosin light chain or of myosin light chain phosphatase regulatory subunit. Using ultracentrifugation and confocal microscopy, we found that AMPK induced depolymerization of F-actin (filamentous actin). Imaging of arteries from LifeAct mice showed F-actin rarefaction in the midcellular portion of VSM. Immunoblotting revealed that this was associated with activation of the actin severing factor cofilin. Coimmunoprecipitation experiments indicated that AMPK leads to the liberation of cofilin from 14-3-3 protein. Conclusions: AMPK induces actin depolymerization, which reduces vascular tone and the response to vasoconstrictors. Our findings demonstrate a new role of AMPK in the control of actin cytoskeletal dynamics, potentially allowing for long-term dilation of microvessels without substantial changes in cytosolic Ca2+.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schubert, Kai Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Qiu, Jiehua UNSPECIFIED UNSPECIFIED UNSPECIFIED Blodow, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiedenmann, Margarethe UNSPECIFIED UNSPECIFIED UNSPECIFIED Lubomirov, Lubomir T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfitzer, Gabriele UNSPECIFIED UNSPECIFIED UNSPECIFIED Pohl, Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneider, Holger UNSPECIFIED orcid.org/0000-0003-1556-0951 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-225089
DOI:	10.1161/CIRCRESAHA.116.309962
Journal or Publication Title:	Circ.Res.
Volume:	121
Number:	2
Page Range:	S. 149 - 184
Date:	2017
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1524-4571
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VASCULAR SMOOTH-MUSCLE; ACTIVATED PROTEIN-KINASE; CYTOSKELETAL DYNAMICS; HYPERTENSIVE-RATS; CA2+ SENSITIVITY; CELL-MIGRATION; BLOOD-PRESSURE; RHO-KINASE; CONTRACTION; POLYMERIZATION Multiple languages Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22508