Title | Endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing by suppressing oxidative stress in diabetes |
Authors | Tie, Lu Li, Xue-Jun Wang, Xian Channon, Keith M. Chen, Alex F. |
Affiliation | Univ Pittsburgh, Sch Med & Vasc Surg Res, Dept Surg, Dept Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Peking Univ, Sch Basic Med Sci, Dept Pharmacol, Beijing 100871, Peoples R China. Peking Univ, Sch Basic Med Sci, Dept Physiol, Beijing 100871, Peoples R China. Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England. Univ Pittsburgh, Sch Med, Dept Surg, VA Vasc Surg Res,VAPHS, 2W109 151L-U,Univ Dr, Pittsburgh, PA 15240 USA. |
Keywords | tetrahydrobiopterin NITRIC-OXIDE SYNTHASE LOW-RENIN HYPERTENSION IMPAIRED SKIN REPAIR GENE-TRANSFER TETRAHYDROBIOPTERIN DEFICIENCY DEPENDENT RELAXATION MICE ENOS DYSFUNCTION EXPRESSION |
Issue Date | 2009 |
Publisher | american journal of physiology endocrinology and metabolism |
Citation | AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM.2009,296,(6),E1423-E1429. |
Abstract | Tie L, Li XJ, Wang X, Channon KM, Chen AF. Endothelium-specific GTP cyclohydrolase I overexpression accelerates refractory wound healing by suppressing oxidative stress in diabetes. Am J Physiol Endocrinol Metab 296: E1423-E1429, 2009. First published March 31, 2009; doi: 10.1152/ajpendo.00150.2009.-Refractory wound is a severe complication that leads to limb amputation in diabetes. Endothelial nitric oxide synthase (eNOS) plays a key role in normal wound repair but is uncoupled in streptozotocin (STZ)-induced type 1 diabetes because of reduced cofactor tetrahydrobiopterin (BH4). We tested the hypothesis that overexpression of GTP cyclohydrolase I (GTPCH I), the rate-limiting enzyme for de novo BH4 synthesis, retards NOS uncoupling and accelerates wound healing in STZ mice. Blood glucose levels were significantly increased in both male endothelium-specific GTPCH I transgenic mice (Tg-GCH; via a tie-2 promoter) and wild-type (WT) littermates 5 days after STZ regimen. A full-thickness excisional wound was created on mouse dorsal skin by a 4-mm punch biopsy. Wound closure was delayed in STZ mice, which was rescued in STZ Tg-GCH mice. Cutaneous BH4 level was significantly reduced in STZ mice vs. WT mice, which was maintained in STZ Tg-GCH mice. In STZ mice, constitutive NOS (cNOS) activity and nitrite levels were decreased compared with WT mice, paralleled by increased superoxide anion (O-2(-)) level and inducible NOS (iNOS) activity. In STZ Tg-GCH mice, nitrite level and cNOS activity were potentiated and O-2(-) level and iNOS activity were suppressed compared with STZ mice. Thus endothelium-specific BH4 overexpression accelerates wound healing in type 1 diabetic mice by enhancing cNOS activity and suppressing oxidative stress. |
URI | http://hdl.handle.net/20.500.11897/396376 |
ISSN | 0193-1849 |
DOI | 10.1152/ajpendo.00150.2009 |
Indexed | SCI(E) |
Appears in Collections: | 基础医学院 |