%0 Journal Article
%T 4-Hydroxy-2-Nonenal-Modified Glyceraldehyde-3-Phosphate Dehydrogenase Is Degraded by Cathepsin G in Rat Neutrophils
%A Yukihiro Tsuchiya
%A Go Okada
%A Shigeki Kobayashi
%A Toshiyuki Chikuma
%A Hiroshi Hojo
%J Oxidative Medicine and Cellular Longevity
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/213686
%X Degradation of oxidized or oxidatively modified proteins is an essential part of the antioxidant defenses of cells. 4-Hydroxy-2-nonenal, a major reactive aldehyde formed by lipid peroxidation, causes many types of cellular damage. It has been reported that 4-hydroxy-2-nonenal-modified proteins are degraded by the ubiquitin-proteasome pathway or, in some cases, by the lysosomal pathway. However, our previous studies using U937 cells showed that 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase is degraded by cathepsin G. In the present study, we isolated the 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase-degrading enzyme from rat neutrophils to an active protein fraction of 28£¿kDa. Using the specific antibody, the 28£¿kDa protein was identified as cathepsin G. Moreover, the degradation activity was inhibited by cathepsin G inhibitors. These results suggest that cathepsin G plays a crucial role in the degradation of 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase. 1. Introduction Low-to-moderate concentrations of reactive oxygen species affect a great number of physiological functions. However, when the reactive oxygen species concentration exceeds the antioxidative capacity of an organism, animal cells enter a state termed oxidative stress, in which the excess reactive oxygen species induces oxidative damage on cellular components. As a result, oxidative stress has been implicated in a large range of diseases, including cancer, diabetes, male infertility, autoimmune diseases, atherosclerosis, and cardiovascular disorders [1¨C3]. Exposure to oxidative stress, which occurs in the presence of reactive oxygen species and free radicals, causes many adverse events including modification of proteins and reactions with DNA [4]. Lipid peroxidation also occurs, and various reactive aldehydes, such as 2-alkenals, 4-hydroxy-2-alkenals, and ketoaldehydes, are generated [5]. 4-Hydroxy-2-nonenal (HNE) is a major reactive aldehyde formed by the peroxidation of ¦Ø-6 polyunsaturated fatty acids, such as linoleic acid and arachidonic acid [6], and is involved in various physiological and pathological reactions [5, 6]. HNE has a high stability and reactivity and is largely responsible for many types of cellular damage associated with oxidative stress. HNE covalently binds to cysteine, lysine, or histidine residues [5]. These adducts are detected in several disease lesions, including in the brains of patients with Alzheimer¡¯s disease [7, 8] and in low-density lipoproteins of atherosclerotic lesions [9]. HNE
%U http://www.hindawi.com/journals/omcl/2011/213686/