Universität zu Köln

Lubomirov, Lubomir T., Gagov, Hristo, Schroeter, Mechthild M., Wiesner, Rudolf J. and Franko, Andras ORCID: 0000-0003-0485-5439 (2019). Augmented contractility of murine femoral arteries in a streptozotocin diabetes model is related to increased phosphorylation of MYPT1. PHYSIOL. REP., 7 (3). HOBOKEN: WILEY. ISSN 2051-817X

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Abstract

Diabetes mellitus (DM) is a metabolic disorder with high prevalence, and a major risk factor for macro- and microvascular abnormalities. This study was undertaken to explore the mechanisms of hypercontractility of murine femoral arteries (FA) obtained from mice with streptozotocin (STZ)-induced diabetes and its relation to the phosphorylation profile of the myosin phosphatase target subunit 1, MYPT1. The immunoreactivity of MYPT1 toward phospho-MYPT1-T696, MYPT1-T853, or MYPT1-S695, used as a read out for MYPT1 phosphorylation, has been studied by Western Blotting. Contractile activity of FA from control and STZ mice has been studied by wire myography. At basal conditions (no treatment), the immunoreactivity of MYPT1-T696/T853 was similar to 2-fold higher in the STZ arteries compared with controls. No changes in MYPT1-T696/853 phosphorylation were observed after stimulation with the Thromboxan-A(2) analog, U46619. Neither basal nor U46619-stimulated phosphorylation of MYPT1 at S695 was affected by STZ treatment. Mechanical distensibility and basal tone of FA obtained from STZ animals were similar to controls. Maximal force after treatment of FA with the contractile agonists phenylephrine (10 mu mol/L) or U46619 (1 mu mol/L) was augmented in the arteries of STZ mice by similar to 2- and similar to 1.5-fold, respectively. In summary, our study suggests that development of a hypercontractile phenotype in murine FA in STZ diabetes is at least partially related to an increase in phosphorylation of MLCP at MYPT1-T696/853. Interestingly, the phosphorylation at S695 site was not altered in STZ-induced diabetes, supporting the view that S695 may serve as a sensor for mechanical activity which is not directly involved in tone regulation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lubomirov, Lubomir T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gagov, Hristo UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Mechthild M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Franko, Andras UNSPECIFIED orcid.org/0000-0003-0485-5439 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-157911
DOI:	10.14814/phy2.13975
Journal or Publication Title:	PHYSIOL. REP.
Volume:	7
Number:	3
Date:	2019
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2051-817X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LIGHT-CHAIN PHOSPHATASE; TARGETING SUBUNIT-1 PHOSPHORYLATION; VASCULAR SMOOTH-MUSCLE; RHO-ASSOCIATED KINASE; ENDOTHELIAL DYSFUNCTION; CA2+ SENSITIZATION; CAROTID ARTERIES; RAT MODELS; IN-VIVO; MYOSIN Multiple languages Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15791