کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8450333 1547682 2018 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Activated mitochondrial apoptosis in hESCs after dissociation involving the PKA/p-p53/Bax signaling pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Activated mitochondrial apoptosis in hESCs after dissociation involving the PKA/p-p53/Bax signaling pathway
چکیده انگلیسی
Human embryonic stem cells (hESCs) are highly fragile with massive cell death after dissociation into single cells, which seriously hampers their applications. The mechanism underlying the massive cell death after dissociation still remains elusive. Here, the expression of apoptosis-related proteins, cell survival and mitochondrial membrane potential in dissociated hESCs before and after the treatments with a protein kinase A (PKA) inhibitor H89 and p53 inhibitor Pifithrin α were investigated, respectively. Protein interactions were identified by immunoprecipitation and immunofluorescence. The results show that the dissociation causes Caspase-dependent apoptosis in hESCs mediated by mitochondrial pathway with the up-regulation of pro-apoptotic proteins, decrease in mitochondrial membrane potential and elevation in pro-apoptotic Cyto c release, which are obviously suppresses by H89. The dissociation-induced increase of phosphorylated p53 Ser15 (p-p53) is suppressed by Pifithrin α which also rescues the elevated levels of pro-apoptotic proteins in mitochondrial pathway. During the dissociation-induced apoptosis, PKA/p-p53/Bax signaling pathway is identified by immunoprecipitation and immunofluorescence showing the most likely interaction between them. These results indicate that dissociation induces mitochondrial apoptosis in hESCs involving PKA/p-p53/Bax signaling pathway, which not only give new insights into the apoptosis mechanism of dissociated hESCs, but also provide clues for developing potential strategies to promote hESC survival after dissociation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 369, Issue 2, 15 August 2018, Pages 226-233
نویسندگان
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