DNAJB3/HSP-40 cochaperone is downregulated in obese humans and is restored by physical exercise.
DNAJB3/HSP-40 cochaperone is downregulated in obese humans and is restored by physical exercise.
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DOI：
10.1371/journal.pone.0069217
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dehbi M
中科院分区：
文献类型：
--
作者：
Abubaker J;Tiss A;Abu-Farha M;Al-Ghimlas F;Al-Khairi I;Baturcam E;Cherian P;Elkum N;Hammad M;John J;Kavalakatt S;Khadir A;Warsame S;Dermime S;Behbehani K;Dehbi M
肥胖是导致胰岛素抵抗和糖尿病等多种疾病的主要危险因素。这些慢性疾病的潜在机制是复杂的，但低度炎症和内源性应激防御系统的改变是公认的。先前的研究表明，HSP-25和HSP-72的损伤与人类和动物的肥胖、胰岛素抵抗和糖尿病有关，而它们的诱导与改善的临床结果有关。在试图确定可能由肥胖失调的热休克反应的其他成分中，我们使用了RT 2-Profiler PCR热休克阵列，辅以RT-PCR，并通过Western印迹和免疫组织化学进行验证。使用非糖尿病瘦型和肥胖受试者的脂肪组织活检和PBMC，我们报告了肥胖者中DNAJB 3辅伴侣蛋白mRNA和蛋白的下调，其与体脂百分比（P = 0.0001）、甘油三酯（P = 0.035）以及炎性趋化因子IP-10和RANTES（分别为P= 0.036和P =0.02）呈负相关。 DNAJB与最大耗氧量呈正相关（P = 0.031）。 基于体育锻炼的有益效果，我们研究了其对DNAJB 3表达的可能影响，事实上，我们发现运动恢复了肥胖受试者中DNAJB 3的表达，同时磷酸化JNK减少。使用细胞系，DNAJB 3蛋白在用棕榈酸酯和衣霉素处理后减少，这表明DNAJB 3的表达与内质网应激的激活之间的联系。DNAJB 3还显示与JNK和IKKβ应激激酶沿着HSP-72共免疫调节，因此提示其在调节其活性中的潜在作用。总的来说，这些数据表明DNAJB 3可能对肥胖起保护作用。
Obesity is a major risk factor for a myriad of disorders such as insulin resistance and diabetes. The mechanisms underlying these chronic conditions are complex but low grade inflammation and alteration of the endogenous stress defense system are well established. Previous studies indicated that impairment of HSP-25 and HSP-72 was linked to obesity, insulin resistance and diabetes in humans and animals while their induction was associated with improved clinical outcomes. In an attempt to identify additional components of the heat shock response that may be dysregulated by obesity, we used the RT2-Profiler PCR heat shock array, complemented with RT-PCR and validated by Western blot and immunohistochemistry. Using adipose tissue biopsies and PBMC of non-diabetic lean and obese subjects, we report the downregulation of DNAJB3 cochaperone mRNA and protein in obese that negatively correlated with percent body fat (P = 0.0001), triglycerides (P = 0.035) and the inflammatory chemokines IP-10 and RANTES (P = 0.036 and P = 0.02, respectively). DNAJB positively correlated with maximum oxygen consumption (P = 0.031). Based on the beneficial effect of physical exercise, we investigated its possible impact on DNAJB3 expression and indeed, we found that exercise restored the expression of DNAJB3 in obese subjects with a concomitant decrease of phosphorylated JNK. Using cell lines, DNAJB3 protein was reduced following treatment with palmitate and tunicamycin which is suggestive of the link between the expression of DNAJB3 and the activation of the endoplasmic reticulum stress. DNAJB3 was also shown to coimmunoprecipiate with JNK and IKKβ stress kinases along with HSP-72 and thus, suggesting its potential role in modulating their activities. Taken together, these data suggest that DNAJB3 can potentially play a protective role against obesity.
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DOI：
10.1042/bj20111114
发表时间：
2012-05-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Dremina ES;Sharov VS;Schöneich C
通讯作者：
Schöneich C
影响因子：
2
作者：
Furuhashi M;Ishimura S;Ota H;Miura T
通讯作者：
Miura T
影响因子：
16
作者：
Hageman, Jurre;Rujano, Maria A.;Kampinga, Harm H.
通讯作者：
Kampinga, Harm H.
影响因子：
4.8
作者：
Asea, A;Rehli, M;Calderwood, SK
通讯作者：
Calderwood, SK
影响因子：
14.8
作者：
Calamini, Barbara;Silva, Maria Catarina;Madoux, Franck;Hutt, Darren M.;Khanna, Shilpi;Chalfant, Monica A.;Saldanha, S. Adrian;Hodder, Peter;Tait, Bradley D.;Garza, Dan;Balch, William E.;Morimoto, Richard I.
通讯作者：
Morimoto, Richard I.