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The carboxyl terminus of HSP70 interacting protein (CHIP) has been demonstrated to have a protective role in several diseases, including cardiac complications; however, the role in preventing AGE\u2010induced cardiac damages remains poorly understood. Here, we found that elevated AGE levels impaired cardiac CHIP expression in streptozotocin\u2010induced diabetes and high\u2010fat diet\u2010administered animals, representing AGE exposure models. We used the TUNEL assay, hematoxylin and eosin, Masson\u2032s trichrome staining, and western blotting to prove that cardiac injuries were induced in diabetic animals and AGE\u2010treated cardiac cells. Interestingly, our results collectively indicated that CHIP overexpression significantly rescued the AGE\u2010induced cardiac injuries and promoted cell survival. Moreover, CHIP knockdown\u2010mediated stabilization of nuclear factor \u03baB\u00a0(NF\u03baB) was attenuated by overexpressing CHIP in the cells. Furthermore, co\u2010immunoprecipitation and immunoblot assay revealed that CHIP promotes the ubiquitination and proteasomal degradation of AGE\u2010induced NF\u03baB. Importantly, fluorescence microscopy, a luciferase reporter assay, electrophoretic mobility shift assay, and subcellular fractionation further demonstrated that CHIP overexpression inhibits AGE\u2010induced NF\u03baB nuclear translocation, reduced its binding ability with the promoter sequences of the receptor of AGE, consequently inhibiting the translocation of the receptor AGE to the cell membrane for its proper function. Overall, our current study findings suggest that CHIP can target NF\u03baB for ubiquitin\u2010mediated proteasomal degradation, and thereby potentially rescue AGE\u2010induced cardiac damages.<\/jats:p>","DOI":"10.1002\/jcp.30660","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T12:25:26Z","timestamp":1640607926000},"page":"1888-1901","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Carboxyl terminus of HSP70\u2010interacting protein attenuates advanced glycation end products\u2010induced cardiac injuries by promoting NF\u03baB proteasomal degradation"],"prefix":"10.1002","volume":"237","author":[{"given":"Kuan\u2010Ho","family":"Lin","sequence":"first","affiliation":[{"name":"College of Medicine China Medical University Taichung Taiwan"},{"name":"Department of Emergency Medicine China Medical University Hospital Taichung 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