| Amelioration of Diabetic Neuropathy by TAT-Mediated Enhanced Delivery of Metallothionein and SOD. | |
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MedLine Citation:
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PMID: 22128026 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Because diabetic neuropathy (DN) appears to result from oxidative stress in neuronal tissues, antioxidant treatment should counteract the condition. Metallothionein (MT) and superoxide dismutase (SOD) are free-radical scavengers, but their ability to cross biological membranes is limited. Applying cell penetrating peptide technologies, we made Tat-MT and Tat-SOD constructs and tested their ability to protect PC12 cells, as surrogates of peripheral nerve cells, from various forms of oxidative damage. Tat-MT and Tat-SOD were successfully delivered to PC12 cells, and the intracellular activities of MT and SOD increased in line with the amount of protein delivered. These agents inhibited cellular damage and apoptotic signaling caused by three different types of injuries (high glucose, hypoxia, and advanced glycation end product injury). We also examined transduction of Tat-MT and Tat-SOD into Otsuka Long-Evans Tokushima fatty rats. A single ip injection of Tat-MT and Tat-SOD resulted in increased radical scavenging activity and decreased apoptosis, by inhibiting nuclear factor κB and MAPK signaling. Continuous treatment resulted in improved myelination of sciatic nerves and delayed the clinical development of DN. We conclude that effective delivery of a combination antioxidant treatment may facilitate the repair of damage in patients with DN. |
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Authors:
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Dongsoo Min; Hyunok Kim; Leejin Park; Tae Hwa Kim; Sejin Hwang; Mi Jung Kim; Seongho Jang; Yongsoo Park |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-29 |
Journal Detail:
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Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Internal Medicine and Bioengineering (D.M., H.K., L.P., T.H.K., Y.P.), Hanyang University College of Medicine and Engineering; and Departments of Anatomy and Cell Biology (S.H.) and Rehabilitation Medicine (J.K., S.J.), Hanyang University College of Medicine, Seoul 133-791, Korea. |
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