Tagliavacca Luigina, Caretti Anna, Bianciardi Paola, Samaja Michele
Department of Medicine, Surgery and Dentistry, University of Milan, San Paolo Hospital, Milan, Italy.
Biochim Biophys Acta. 2012 Jul;1820(7):900-6. doi: 10.1016/j.bbagen.2012.02.016. Epub 2012 Mar 17.
Low oxygen (O2) availability, a condition called hypoxia, has different and profound consequences in tissues and organs. Besides the hypoxia-inducible response, mammalian cells induce a coordinated cytoprotective pathway called Unfolded Protein Response (UPR). We studied the molecular basis of UPR and apoptosis in animal models exposed to different hypoxic stresses and assessed the ability of liver and myocardium to respond to low oxygen by activating different arms of the UPR according to the severity of the insults in a tissue specific manner.
We assessed the levels of several UPR markers in hypoxic animals by Real Time PCR and Western blotting.
While the hepatocytes activate the apoptotic pathway mediated, in part, by CHOP and p-JNK, we could not detect an UPR-dependent apoptosis in myocytes. Moreover, severe hypoxia results in ATF4 translation, and induction of CHOP and GADD34 transcripts in liver, by contrast in the myocardium, the ATF4-CHOP-GADD34 signaling pathway is not detectably activated.
Comparison of several UPR markers in liver and myocardium enabled to underscore the ability of hepatocytes and myocites to selectively activate and fine tune the UPR signaling pathway during hypoxia in vivo.
低氧状态，即一种称为缺氧的情况，在组织和器官中会产生不同且深远的影响。除了缺氧诱导反应外，哺乳动物细胞还会诱导一种称为未折叠蛋白反应（UPR）的协调细胞保护途径。我们研究了暴露于不同缺氧应激的动物模型中UPR和细胞凋亡的分子基础，并评估了肝脏和心肌根据组织特异性损伤的严重程度通过激活UPR的不同分支来应对低氧的能力。
我们通过实时PCR和蛋白质印迹法评估了缺氧动物中几种UPR标志物的水平。
虽然肝细胞激活了部分由CHOP和p-JNK介导的凋亡途径，但我们在心肌细胞中未检测到UPR依赖性凋亡。此外，严重缺氧导致肝脏中ATF4的翻译以及CHOP和GADD34转录本的诱导，相比之下，在心肌中，ATF4-CHOP-GADD34信号通路未被明显激活。
比较肝脏和心肌中的几种UPR标志物能够突出肝细胞和心肌细胞在体内缺氧期间选择性激活和微调UPR信号通路的能力。
