Universität zu Köln

Romanski, S., Stamellou, E., Jaraba, J. T., Storz, D., Kraemer, B. K., Hafner, M., Amslinger, S., Schmalz, H. G. and Yard, B. A. (2013). Enzyme-triggered CO-releasing molecules (ET-CORMs): Evaluation of biological activity in relation to their structure. Free Radic. Biol. Med., 65. S. 78 - 89. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1873-4596

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Abstract

Acyloxydiene-Fe(CO)(3) complexes act as enzyme-triggered CO-releasing molecules (ET-CORMs) and can deliver CO intracellularly via esterase-mediated hydrolysis. The protective properties of structurally different ET-CORMs on hypothermic preservation damage and their ability to inhibit VCAM-1 expression were tested on cultured human umbilical vein endothelial cells (HUVEC) and renal proximal tubular epithelial cells (PTEC) using a structure-activity approach. Cytotoxicity of ET-CORMs, protection against hypothermic preservation damage, and inhibition of VCAM-1 expression were assessed. Cytotoxicity of 2-cyclohexenone and 1,3-cyclohexanedione-derived ET-CORMs was more pronounced in HUVEC compared to PTEC and was dependent on the position and type of the ester (acyloxy) substituent(s) (acetate > pivalate > palmitate). Protection against hypothermic preservation injury was only observed for 2-cyclohexenone-derived ET-CORMs and was not mediated by the ET-CORM decomposition product 2-cyclohexenone itself. Structural requirements for protection by these ET-CORMs were different for HUVEC and PTEC. Protection was affected by the nature of the ester functionality in both cell lines. VCAM-1 expression was inhibited by both 2-cyclohexenone- and 1,3-cyclohexanedione-derived ET-CORMs. 2-Cyclohexenone, but not 1,3-cyclohexanedione, also inhibited VCAM-1 expression. We demonstrate that structural alterations of ET-CORMs significantly affect their biological activity. Our data also indicate that different ET-CORMs behave differently in various cell types (epithelial vs endothelial). These findings warrant further studies not only to elucidate the structure-activity relation of ET-CORMs in mechanistic terms but also to assess if structural optimization will yield ET-CORMs with restricted cell specificity. (C) 2013 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Romanski, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamellou, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Jaraba, J. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Storz, D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kraemer, B. K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hafner, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Amslinger, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmalz, H. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yard, B. A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-471451
DOI:	10.1016/j.freeradbiomed.2013.06.014
Journal or Publication Title:	Free Radic. Biol. Med.
Volume:	65
Page Range:	S. 78 - 89
Date:	2013
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1873-4596
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CARBON-MONOXIDE; ISCHEMIA/REPERFUSION INJURY; INTIMAL HYPERPLASIA; ENDOTHELIAL-CELLS; CATALYTIC IRON; PRESERVATION; TRANSPLANTATION; EXPRESSION; MECHANISM; INSIGHTS Multiple languages Biochemistry & Molecular Biology; Endocrinology & Metabolism Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/47145