کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8553336 | 1562584 | 2018 | 29 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Gap junctional intercellular communication and endoplasmic reticulum stress regulate chronic cadmium exposure induced apoptosis in HK-2 cells
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کلمات کلیدی
UPRXBP-1sASK1GJICAKT signaling - AKT سیگنالینگIRE1α - IRE1aROS - ROSinositol-requiring enzyme 1 - آنزیم مورد نیاز inositol 1Akt - آکتgap junctional intercellular communication - ارتباط بین سلولی بین دو سلولیER stress - استرس است18α-glycyrrhetinic acid - اسید 18α-گلیسیروتئینیکHK-2 cells - سلول های HK-2endoplasmic reticulum - شبکه آندوپلاسمی Unfolded protein response - پاسخ پروتئین آشکارprotein kinase B - پروتئین کیناز BCadmium - کادمیمapoptosis signal-regulating kinase 1 - کیناز تنظیم کننده سیگنال آپوپتوز 1Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cadmium (Cd), a toxic heavy metal, is known to induce renal toxicity by primarily targeting at renal proximal tubule. Endoplasmic reticulum (ER) stress and gap junctional intercellular communication (GJIC) regulate many pathophysiological processes. Yet, how ER stress and GJIC regulate Cd-induced nephrotoxicity remain elusive. In this study, we treated human proximal tubule (HK-2) cells with 1â¯Î¼M CdCl2 every other day for 12â¯days and found that Cd significantly increased cell apoptosis at 10 and 12â¯days. This cytotoxicity correlated with activation of ER stress and apoptotic signaling evidenced by upregulation of inositol-requiring enzyme 1 (IRE1α), splice X-box binding protein-1 (XBP-1s), and apoptosis signal-regulating kinase 1 (ASK1) proteins. Interestingly, the AKT signaling was activated at 2- and 4-day and then inhibited at 10- and 12-day of Cd treatment; by contrast, Cd decreased GJIC levels at 2- and 4-day followed by a significant increase at 10- and 12-day treatment. Activation of AKT by SC79 or inhibition of GJIC by 18α-glycyrrhetinic acid (18α-GA) completely abolished Cd-induced AKT inhibition and IRE1α-ASK1 activation. Importantly, pretreatment with ER stress inhibitor or 18α-GA significantly mitigated Cd-induced apoptosis. These results suggest that GJIC collaborates with AKT signaling and ER stress in regulating prolonged Cd-treatment-induced apoptosis in HK-2 cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 288, 15 May 2018, Pages 35-43
Journal: Toxicology Letters - Volume 288, 15 May 2018, Pages 35-43
نویسندگان
Zehe Ge, Haipeng Diao, Xiaoli Ji, Qingping Liu, Xiaoyan Zhang, Qing Wu,