کد مقاله کد نشریه سال انتشار مقاله انگلیسی ترجمه فارسی نسخه تمام متن
1904450 1534628 2016 12 صفحه PDF سفارش دهید دانلود رایگان
عنوان انگلیسی مقاله ISI
Modulation of hepatic copper-ATPase activity by insulin and glucagon involves protein kinase A (PKA) signaling pathway
ترجمه فارسی عنوان
مدولاسیون فعالیت مس ATPase کبدی از طریق انسولین و گلوکاگون شامل مسیر سیگنالینگ A (PKA) پروتئین کیناز
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کلمات کلیدی
نمک هیدروکلراید تریاتیلنتترامین؛ اسید bathocuproinedisulphonic؛ ایزوفرم چرخه‌ای عدم تعادل نوکلئوتید ؛ حمل و نقل مس؛ گلوکاگون؛ انسولین؛ پروتئین کیناز A (PKA)
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
چکیده انگلیسی


• Hepatic copper homeostasis is physiologically balanced by insulin and glucagon.
• The mechanism relies on the modulation of PKA-mediated signaling pathways.
• Insulin stimulates the activity of ATP7B by crosstalk between PI3K-Akt and PKA.
• Glucagon inhibits the activity of ATP7B by activated PKA.

Different studies have revealed copper imbalance in individuals suffering from diabetes and obesity, suggesting that regulation of glucose and/or fat metabolism could modulate cellular copper homeostasis. To test this hypothesis we investigated whether the key hormones of energy metabolism, insulin and glucagon, regulate the functional properties of the major hepatic copper-transporter, ATP7B (i.e., copper-dependent ATPase activity). We demonstrated that insulin reverses the effect of copper and stimulates retrograde trafficking of ATP7B from the canalicular membranes, consistent with the enhanced ability of ATP7B to sequester copper away from the cytosol. Physiological concentrations of insulin increase endogenous ATP7B activity in cultured hepatic cells and in tissues by 40%, whereas glucagon inhibits this activity by 70%. These effects were cancelled out when insulin and glucagon were combined. We also demonstrated that the opposite effects of the hormones on ATP7B activity involve receptor-mediated signaling pathways and membrane-bound kinases (PKA and PKB/Akt), which are reciprocally regulated by insulin and glucagon. Inhibiting insulin signaling at the level of its Tyr-kinase receptor, PI3K or PKB/Akt restored the basal activity of ATP7B. Insulin reduced endogenous PKA activity, whereas glucagon promoted PKA stimulation by approximately 100%. These findings demonstrate that the physiological modulation of ATP7B activity is linked to energy metabolism via insulin and glucagon, and could help to understand the mechanisms involved in the disruption of copper homeostasis in diabetic and obese patients.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 11, November 2016, Pages 2086–2097
نویسندگان
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