Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: The distinct role of protein kinase C and mitochondrial superoxide production

Quagliaro, Lisa; Piconi, Ludovica; Assaloni, Roberta; Da Ros, Roberto; Maier, Amabile; Zuodar, Gianni; Ceriello, Antonio

doi:10.1016/j.atherosclerosis.2005.03.015

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Volume 183, Issue 2 , Pages 259-267, December 2005

Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: The distinct role of protein kinase C and mitochondrial superoxide production

Lisa Quagliaro
- Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy
Ludovica Piconi
- Morpurgo-Hofman Research Laboratory on Aging, Udine, Italy
Roberta Assaloni
- Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Chair of Internal Medicine, P.le S. Maria Della Misericordia, 33100 Udine, Italy
Roberto Da Ros
- Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Chair of Internal Medicine, P.le S. Maria Della Misericordia, 33100 Udine, Italy
Amabile Maier
- Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Chair of Internal Medicine, P.le S. Maria Della Misericordia, 33100 Udine, Italy
Gianni Zuodar
- Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Chair of Internal Medicine, P.le S. Maria Della Misericordia, 33100 Udine, Italy
Antonio Ceriello
- Department of Pathology and Medicine, Experimental and Clinical, University of Udine, Chair of Internal Medicine, P.le S. Maria Della Misericordia, 33100 Udine, Italy
- Corresponding author. Tel.: +39 0432 559813; fax: +39 0432 42097.

Received 13 October 2004; received in revised form 14 March 2005; accepted 21 March 2005.

Abstract

In this study the effects of stable and intermittent high glucose concentrations on ICAM-1, VCAM-1 and E-selectin production, PKC activity and PKCβI, βII and δ isoforms expression in cultured HUVEC have been examined. In stable high glucose ICAM-1, VCAM-1 and E-selectin concentration and mRNA expression increased, and this effect was even more evident in intermittent high glucose. PKC activity increased in fluctuating glucose compared to stable high glucose, due to an over-expression of βI, βII and δ isoforms. ICAM-1, VCAM-1 and E-selectin, after the adding of total PKC inhibitor bisindolylmaleimide-I (BIMI-I) and LY379196, a specific inhibitor of PKCβ, were equally reduced. 8-Hydroxydeoxyguanosine (8-OHdG), a sensitive indicator of oxidative damage to DNA, increased in stable and even more in intermittent high glucose and was reduced by both BIMI-I and LY379196. However, when thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial complex II and the SOD mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) were added, all adhesion molecules, any PKC isoforms expression and 8-hydroxydeoxyguanosine were normalized in both constant and oscillating glucose.

In conclusion intermittent high glucose induces a greater expression of the adhesion molecules than stable high glucose; this effect seems to be related to an activation of PKCβ, but completely dependent from mitochondrial free radicals over-production.

Keywords: Intermittent glucose, Endothelium, Adhesion molecules, PKC, Mitochondrial superoxide