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The bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning.

ABSTRACT: Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC), we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic parameters with levels of ferritin, the main iron storage and detoxifying protein, without and with inhibitors of protein degradation, substantiated this explanation. Diabetic hearts were less sensitive to ischemia-reperfusion stress, as indicated by functional parameters and histology. Mechanistically, since ferritin has been shown to provide cellular protection against insults, including ischemia-reperfusion stress and as the basal ferritin level in diabetic heart was 2-fold higher than in controls, these are in accord with the greater resistance of the diabetic heart to ischemia-reperfusion. Additionally, during ischemia-reperfusion, preceded by IPC, a rapid and extensive loss in ferritin levels, during the prolonged ischemia, in diabetic heart but not in non-diabetic controls, provide additional substantiation to the explanation for loss of respond to IPC. Current research is shedding light on the mechanism behind ferritin degradation as well, suggesting a novel explanation for diabetes-induced loss of cardioprotection.

SUBMITTER: Vinokur V

PROVIDER: S-EPMC3655153 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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The bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning.

Vinokur Vladimir V Berenshtein Eduard E Bulvik Baruch B Grinberg Leonid L Eliashar Ron R Chevion Mordechai M

PloS one 20130515 5

Cardiovascular dysfunction is a major complication of diabetes. Examining mechanistic aspects underlying the incapacity of the diabetic heart to respond to ischemic preconditioning (IPC), we could show that the alterations in iron homeostasis can explain this phenomenon. Correlating the hemodynamic parameters with levels of ferritin, the main iron storage and detoxifying protein, without and with inhibitors of protein degradation, substantiated this explanation. Diabetic hearts were less sensiti ...[more]

PMID: 23690966

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Project description:Humans will eat almost anything, from caribou livers to rutabagas, but there are some types of foods, and their associated taste qualities, that are preferred by large groups of people regardless of culture or experience. When many choices are available, humans chose foods that taste good, that is, create pleasing sensations in the mouth. The concept of good taste for most people encompasses both flavor and texture of food, and these sensations merge with taste proper to form the concept of goodness. Although we acknowledge the universality of the goodness (sweet) or badness (bitter) of basic taste qualities, we also find that people differ, sometimes extremely so, in their ability to perceive and enjoy these qualities and, by extension, food and drink. The reasons for these differences among people are not clear but are probably due to a combination of experience beginning at an early age, perhaps in utero; learning, for example, as with conditioned taste aversions; sex and maturity; and perceptual differences that arise from genetic variation. In this review, we focus on individual variations that arise from genetic differences and review two domains of science: recent developments in the molecular biology of taste transduction, with a focus on the genes involved and second, studies that examine biological relatives to determine the heritability of taste perception. Because the receptors for sweet, savory (umami), and bitter have recently been discovered, we summarize what is known about their function by reviewing the effect of naturally occurring and man-made alleles of these receptors, their shape and function based on receptor modeling techniques, and how they differ across animal species that vary in their ability to taste certain qualities. We discuss this literature in the context of how taste genes may differ among people and give rise to individuated taste experience, and what is currently known about the genetic effects on taste perception in humans.

Dataset Information

The bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning.

Publications

The bitter fate of the sweet heart: impairment of iron homeostasis in diabetic heart leads to failure in myocardial protection by preconditioning.

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