کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10759220 | 1050417 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Critical contribution of oxidative stress to TNFα-induced necroptosis downstream of RIPK1 activation
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کلمات کلیدی
TNFαBHAFADDRipk1TRADDcIAP1necrostatin-1TNFTNF receptor-associated death domaincellular inhibitor of apoptosis protein-1Nec-1 - NEC-1Oxidative stress - تنش اکسیداتیوtumor necrosis factor - فاکتور نکروز تومورNecroptosis - نئروپتوزیسbutylated hydroxyanisole - هیدروکسی آنیزول باتلاقیFas-associated protein with death domain - پروتئین مرتبط با Fas با دامنه مرگ
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
While apoptosis has been considered to be identical to programmed cell death, necroptosis, which is morphologically related to necrosis, has emerged as a novel type of programmed cell death. Necroptosis depends on two structurally related kinases, receptor-interacting serine-threonine kinase (RIPK)1 and RIPK3. RIPK1 is activated through oligomerization of upstream adaptor molecules such as Fas-associated protein with death domain (FADD) and TNF receptor-associated death domain (TRADD) that are triggered by TNFα or Fas ligand. Activated RIPK1 subsequently interacts with and activates RIPK3, resulting in necroptosis. However, contribution of oxidative stress to execution of necroptosis is still controversial. We found that a selective inhibitor for RIPK1, necrostatin-1 (Nec-1) significantly blocked TNFα-induced cell death and ROS accumulation in NF-κB activation-deficient cells. This suggests that these cells mostly died by necroptosis upon TNFα stimulation. Intriguingly, an antioxidant, butylated hydroxyanisole (BHA) blocked TNFα-induced necroptosis and ROS accumulation in NF-κB activation-deficient cells. However, Nec-1, but not BHA, inhibited TNFα-induced phosphorylation of RIPK1 in these cells, suggesting that ROS play a crucial role in execution of necroptosis downstream of RIPK1 activation. Structural and functional analyses using BHA related compounds revealed that both tert-butyl and hydroxy groups of BHA are crucial for its anti-necroptotic function. Together, these results suggest that TNFα-induced necroptosis is tightly associated with oxidative stress, and oxidative stress is induced downstream of RIPK1 activation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 436, Issue 2, 28 June 2013, Pages 212-216
Journal: Biochemical and Biophysical Research Communications - Volume 436, Issue 2, 28 June 2013, Pages 212-216
نویسندگان
Ryodai Shindo, Hidenao Kakehashi, Ko Okumura, Yoshito Kumagai, Hiroyasu Nakano,