AIM: This study was investigated to characterize the activation mechanism of a mitogen-activated protein (MAP) kinase superfamily in diabetes in aortae and cultured vascular smooth muscle cells (VSMCs) from rats. METHODS: Male Sprague-Dawley rats were used for this procedure, and diabetes was induced by streptozotocin injection at 50 mg/kg. After 6 weeks, the thoracic aortae from normal and diabetic rats were removed for detection of the MAP kinase superfamily by immunoblot analysis. RESULTS: In aortae, the protein levels of extracellular signal-regulated protein kinase (ERK)-1, c-jun NH2-terminal protein kinase (JNK)-1 and -2, and p38 increased significantly more in diabetic rats than in normal rats. In contrast, phosphorylated protein levels of ERK-1 and -2, JNK-1, and p38 were significantly more elevated in diabetic rats than in normal rats. In VSMCs from normal rats, a high concentration of glucose cultured for three days significantly increased the phosphorylated protein levels of ERKs and p38, but not JNKs, without any change of these protein levels. Serum interleukin (IL)-1beta was significantly higher in diabetic rats than in normal rats. Several types of proinflammatory cytokine dose-dependently phosphorylated the levels of ERKs, JNK-1, and p38, but not JNK-2, in VSMCs from normal rats. In cells from diabetic rats, phosphorylated protein levels of ERKs and p38 were significantly elevated by IL-1beta. In addition, interferon-gamma phosphorylated the levels of ERKs in diabetic cells more than in normal cells. CONCLUSION: Our results suggest that, under diabetic conditions, the MAP kinase superfamily was activated by different pathways in the vasculature; i.e., ERKs and p38 might be mainly phosphorylated by a complex of high concentrations of glucose and of several types of proinflammatory cytokines, but the phosphorylation of JNK-1 might depend on the concentration of proinflammatory cytokines such as IL-1beta, and/or additional unknown factors, except glucose.
AIM: This study was investigated to characterize the activation mechanism of a mitogen-activated protein (MAP) kinase superfamily in diabetes in aortae and cultured vascular smooth muscle cells (VSMCs) from rats. METHODS: Male Sprague-Dawley rats were used for this procedure, and diabetes was induced by streptozotocin injection at 50 mg/kg. After 6 weeks, the thoracic aortae from normal and diabeticrats were removed for detection of the MAP kinase superfamily by immunoblot analysis. RESULTS: In aortae, the protein levels of extracellular signal-regulated protein kinase (ERK)-1, c-jun NH2-terminal protein kinase (JNK)-1 and -2, and p38 increased significantly more in diabeticrats than in normal rats. In contrast, phosphorylated protein levels of ERK-1 and -2, JNK-1, and p38 were significantly more elevated in diabeticrats than in normal rats. In VSMCs from normal rats, a high concentration of glucose cultured for three days significantly increased the phosphorylated protein levels of ERKs and p38, but not JNKs, without any change of these protein levels. Serum interleukin (IL)-1beta was significantly higher in diabeticrats than in normal rats. Several types of proinflammatory cytokine dose-dependently phosphorylated the levels of ERKs, JNK-1, and p38, but not JNK-2, in VSMCs from normal rats. In cells from diabeticrats, phosphorylated protein levels of ERKs and p38 were significantly elevated by IL-1beta. In addition, interferon-gamma phosphorylated the levels of ERKs in diabetic cells more than in normal cells. CONCLUSION: Our results suggest that, under diabetic conditions, the MAP kinase superfamily was activated by different pathways in the vasculature; i.e., ERKs and p38 might be mainly phosphorylated by a complex of high concentrations of glucose and of several types of proinflammatory cytokines, but the phosphorylation of JNK-1 might depend on the concentration of proinflammatory cytokines such as IL-1beta, and/or additional unknown factors, except glucose.
Authors: Surabhi Chandra; David J R Fulton; Ruth B Caldwell; R William Caldwell; Haroldo A Toque Journal: Eur J Pharmacol Date: 2018-11-28 Impact factor: 4.432
Authors: Yunpeng Du; Jie Tang; Guangyuan Li; Guanyuan Li; Liliana Berti-Mattera; Chieh Allen Lee; Darian Bartkowski; David Gale; Joe Monahan; Michael R Niesman; Gordon Alton; Timothy S Kern Journal: Invest Ophthalmol Vis Sci Date: 2010-01-13 Impact factor: 4.799