Browsing by Subject "4-HNE"

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    Protein carbonylation in the adipocyte nucleus
    (2017-11) Hauck, Amy
    As the incidence of obesity rises globally, it has become increasingly imperative to identify the mechanisms that cause obesity-related metabolic disease. In particular, oxidative stress in the adipose tissue is known to cause metabolic dysfunction, but the mechanisms that contribute to this process remain unclear. Protein carbonylation refers to the post-translational modification of lysine, cysteine, and histidine residues by diffusible electrophilic lipids. Specifically, 4- hydroxy-2-nonenal (4-HNE) and 4-hydroxy-2-hexenal (4-HHE) are produced at high levels in obese adipose tissue as a direct result of increased oxidative stress. The studies herein focus on the hypothesis that protein carbonylation is a mechanistic link between elevated oxidative stress and metabolic dysfunction in obese adipose tissue. We found that protein carbonylation is elevated specifically in the nucleus of adipocytes as a consequence of obesity and of aging. Proteomic evaluation of these modifications revealed that the core histones and zinc finger proteins are major targets of carbonylation. Since these proteins are critical regulators of transcriptional mechanisms, these data describe a potential link between oxidative stress and altered expression of metabolic pathways in adipose tissue.