A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic pe...A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic peripheral neuropathy. Therefore, this study investigated the effects of high glucose on proliferation, apoptosis, and 3-nitrotyrosine levels of Schwann cells treated with butylphthalide. In addition, we explored potential protective mechanisms of butylphthalide on peripheral nerves. Schwann cells were cultured in vitro with high glucose then stimulated with the peroxynitrite anion inhibitors uric acid and 3-n-butylphthalide for 48 hours. Cell Counting Kit-8 and flow cytometry were used to investigate the effects of uric acid and 3-n-butylphthalide on proliferation and apoptosis of Schwann cells exposed to a high glucose environment. Effects of uric acid and 3-n-butylphthalide on levels of 3-nitrotyrosine in Schwann cells were detected by enzyme-linked immunosorbent assay. The results indicated that Schwann cells cultured in high glucose showed decreased proliferation, but increased apoptosis and intracellular 3-nitrotyrosine levels. However, intervention with uric acid or 3-n-butylphthalide could increase proliferation of Schwann cells cultured in high glucose, and inhibited apoptosis and intracellular 3-nitrotyrosine levels. According to our data, 3-n-butylphthalide may inhibit cell nitrification and apoptosis, and promote cell proliferation, thereby reducing damage to Schwann cells caused by high glucose.展开更多
AIM: Experimental studies suggest that free radicals are involved in acid and pepsin-induced damage of esophageal mucosa. The profile and balance between free radicals and antioxidant systems in human esophagitis are ...AIM: Experimental studies suggest that free radicals are involved in acid and pepsin-induced damage of esophageal mucosa. The profile and balance between free radicals and antioxidant systems in human esophagitis are unknown. METHODS: Superoxide anion and its powerful oxidant reaction with nitric oxide (peroxynitrite) generation were determined in esophageal mucosal biopsies from 101 patients with different gastro-esophageal reflux diseases and 28 controls. Activity of both superoxide dismutase (SOD) and catalase, and reduced glutathione (GSH) levels, were also assessed. Expression of Cu,ZnSOD, MnSOD and tyrosine-nitrated MnSOD were analyzed by Western blot and/or immunohistochemistry. RESULTS: The highest levels of superoxide anion generation were found in patients with severe lesions of esophagitis. Peroxynitrite generation was intense in Barrett's biopsies, weaker in esophagitis and absent/weak in normal mucosa. Expression of Cu,ZnSOD and MnSOD isoforms were present in normal mucosa and increased according to the severity of the lesion, reaching the highest level in Barrett's esophagus. However, SOD mucosal activity significantly decreased in patients with esophagitis and Barrett's esophagus, which was, at least in part, due to nitration of its tyrosine residues. Catalase activity and GSH levels were significantly increased in mucosal specimens from patients with esophagitis and/or Barrett's esophagus. CONCLUSION: A decrease in SOD antioxidant activity leading to increased mucosal levels of superoxide anion and peroxynitrite radicals may contribute to the development of esophageal damage and Barrett's esophagus in patients with gastroesophageal reflux. Administration of SOD may be a therapeutic target in the treatment of patients with esophagitis and Barrett's esophagus.展开更多
目的探讨丹皮酚拮抗过氧亚硝基阴离子(ONOO-)对体外培养大鼠成骨细胞凋亡的作用。方法用改良的组织块法分离培养新生大鼠颅骨成骨细胞,采用淬灭流动反应方法体外制备ONOO-,以1 mm o l/L终浓度加入成骨细胞培养体系,作用30 m in后弃去,...目的探讨丹皮酚拮抗过氧亚硝基阴离子(ONOO-)对体外培养大鼠成骨细胞凋亡的作用。方法用改良的组织块法分离培养新生大鼠颅骨成骨细胞,采用淬灭流动反应方法体外制备ONOO-,以1 mm o l/L终浓度加入成骨细胞培养体系,作用30 m in后弃去,继续常规培养12 h,用Hoechst33258染色法及TUNEL法检测成骨细胞的凋亡,并以0.1 mm o l/L丹皮酚消除ONOO-(1 mm o l/L)对大鼠成骨细胞凋亡的影响。结果1 mm o l/L的ONOO-可导致大鼠成骨细胞凋亡;0.1 mm o l/L丹皮酚能拮抗ONOO-(1 mm o l/L)所引起的大鼠成骨细胞凋亡。结论丹皮酚0.1 mm o l/L在体外具有拮抗ONOO-(1 mm o l/L)致大鼠成骨细胞凋亡的作用。展开更多
基金supported by grant from Hong Kong RGC General Research Fund(774808M,777610M,777611M)Seed Funding Program for Basic Research the University of Hong Kong(201011159053)~~
基金supported by the Natural Science Foundation of Anhui Province,China,No.1608085MH209(to YBW)New Medicine of University of Science and Techology of China,No.WK110000036(to YBW)
文摘A high glucose state readily causes peripheral axon atrophy, demyelination, loss of nerve fiber function, and delayed regeneration. However, few studies have examined whether nitration is also critical for diabetic peripheral neuropathy. Therefore, this study investigated the effects of high glucose on proliferation, apoptosis, and 3-nitrotyrosine levels of Schwann cells treated with butylphthalide. In addition, we explored potential protective mechanisms of butylphthalide on peripheral nerves. Schwann cells were cultured in vitro with high glucose then stimulated with the peroxynitrite anion inhibitors uric acid and 3-n-butylphthalide for 48 hours. Cell Counting Kit-8 and flow cytometry were used to investigate the effects of uric acid and 3-n-butylphthalide on proliferation and apoptosis of Schwann cells exposed to a high glucose environment. Effects of uric acid and 3-n-butylphthalide on levels of 3-nitrotyrosine in Schwann cells were detected by enzyme-linked immunosorbent assay. The results indicated that Schwann cells cultured in high glucose showed decreased proliferation, but increased apoptosis and intracellular 3-nitrotyrosine levels. However, intervention with uric acid or 3-n-butylphthalide could increase proliferation of Schwann cells cultured in high glucose, and inhibited apoptosis and intracellular 3-nitrotyrosine levels. According to our data, 3-n-butylphthalide may inhibit cell nitrification and apoptosis, and promote cell proliferation, thereby reducing damage to Schwann cells caused by high glucose.
基金Supported by the grant FIS 99/0569 from the Fondo de Investigaciones Sanitarias and Instituto de Salud Carlos Ⅲ (C03/02)
文摘AIM: Experimental studies suggest that free radicals are involved in acid and pepsin-induced damage of esophageal mucosa. The profile and balance between free radicals and antioxidant systems in human esophagitis are unknown. METHODS: Superoxide anion and its powerful oxidant reaction with nitric oxide (peroxynitrite) generation were determined in esophageal mucosal biopsies from 101 patients with different gastro-esophageal reflux diseases and 28 controls. Activity of both superoxide dismutase (SOD) and catalase, and reduced glutathione (GSH) levels, were also assessed. Expression of Cu,ZnSOD, MnSOD and tyrosine-nitrated MnSOD were analyzed by Western blot and/or immunohistochemistry. RESULTS: The highest levels of superoxide anion generation were found in patients with severe lesions of esophagitis. Peroxynitrite generation was intense in Barrett's biopsies, weaker in esophagitis and absent/weak in normal mucosa. Expression of Cu,ZnSOD and MnSOD isoforms were present in normal mucosa and increased according to the severity of the lesion, reaching the highest level in Barrett's esophagus. However, SOD mucosal activity significantly decreased in patients with esophagitis and Barrett's esophagus, which was, at least in part, due to nitration of its tyrosine residues. Catalase activity and GSH levels were significantly increased in mucosal specimens from patients with esophagitis and/or Barrett's esophagus. CONCLUSION: A decrease in SOD antioxidant activity leading to increased mucosal levels of superoxide anion and peroxynitrite radicals may contribute to the development of esophageal damage and Barrett's esophagus in patients with gastroesophageal reflux. Administration of SOD may be a therapeutic target in the treatment of patients with esophagitis and Barrett's esophagus.
文摘目的探讨丹皮酚拮抗过氧亚硝基阴离子(ONOO-)对体外培养大鼠成骨细胞凋亡的作用。方法用改良的组织块法分离培养新生大鼠颅骨成骨细胞,采用淬灭流动反应方法体外制备ONOO-,以1 mm o l/L终浓度加入成骨细胞培养体系,作用30 m in后弃去,继续常规培养12 h,用Hoechst33258染色法及TUNEL法检测成骨细胞的凋亡,并以0.1 mm o l/L丹皮酚消除ONOO-(1 mm o l/L)对大鼠成骨细胞凋亡的影响。结果1 mm o l/L的ONOO-可导致大鼠成骨细胞凋亡;0.1 mm o l/L丹皮酚能拮抗ONOO-(1 mm o l/L)所引起的大鼠成骨细胞凋亡。结论丹皮酚0.1 mm o l/L在体外具有拮抗ONOO-(1 mm o l/L)致大鼠成骨细胞凋亡的作用。
