RSL3 induced autophagic death in glioma cells via causing glycolysis dysfunction
Authors: Guangfan Chi
Chongcheng Wang
Lei Wang
Yinan Luo
Shan Lu
Xuanzhong Wang
Meihua Piao
Chuan He
Pengfei Ge
Journal: Biochemical and biophysical research communications (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Autophagy; Glioma; Glycolysis dysfunction; RSL3.
Affiliations: Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China; Research Center of Neuroscience, First Hospital of Jilin University, Changchun, 130021, China., Department of Anesthesiology, First Hospital of Jilin University, Changchun, 130021, China., Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, 130021, China., Department of Neurosurgery, First Hospital of Jilin University, Changchun, 130021, China; Research Center of Neuroscience, First Hospital of Jilin University, Changchun, 130021, China. Electronic address: .

Abstract:  RSL3 is a type of small molecular compound which can inactivate glutathione peroxidase 4 (GPX4) and induce ferroptosis, but its role in glioma cell death remains unclear. In this study, we found RSL3 inhibited the viabilities of glioma cells and induced glioma cell death in a dose-dependent manner. In vitro studies revealed that RSL3-induced cell death was accompanied with the changes of autophagy-associated protein levels and was alleviated by pretreatment of 3-Methyladenine, bafilomycin A1 and knockdown of ATG5 with siRNA. The ATP and pyruvate content as well as the protein levels of HKII, PFKP, PKM2 were decreased in cells treated by RSL3, indicating that RSL3 induced glycolysis dysfunction in glioma cells. Moreover, supplement of exterior sodium pyruvate, which was a final product of glycolysis, not only inhibited the changes of autophagy-associated protein levels caused by RSL3, but also prevented RSL3-induced cell death. In vivo data suggested that the inhibitory effect of RSL3 on the growth of glioma cells was associated with glycolysis dysfunction and autophagy activation. Taken together, RSL3 induced autophagic cell death in glioma cells via causing glycolysis dysfunction. 

Retracted: No

PubPeer comments:
 In figure 1, 2 and 3, There re a lot of cropping marks that are visible to the naked eye. This kind of image processing makes the details above and below some bands missing, but is misleading and makes people think that they have cropped a larger area from the orginal image. I hope the author can provide the original images.    , 
 Dear Parashorea Tomentella, we cropped the membranes before incubation with primary antibodies in order to save time and antibodies. We are pleased to provide the original images to you, and the other researchers who are interested in this article or these images. Considering that 20 images of western blotting are labeled with green arrowheads, we hope you give us an email address and we will send the original images to you for consideration. Thank you and best wishes for you! Yours sincerely, Pengfei. , 
 #2 Thank you for your prompt reply! What about just show the original image of Figure 1C, U87, u03b2-actin? Because the details above the bands on the right were missing. , 
 Dear Parashorea Tomentella, we past the original image of u03b2-actin here according to your request. Additionally, all the samples used for western blotting analysis have been kept in refrigerators by us. If you were not satisfied with the image pasted below, we would like to perform western blotting again and provide a new one to you. Thank you.  , 
 #4 Thank you very much. , 
 #4 Pengfei Ge, could you kindly indicate, this u03b2-actin image corresponds to which of the u03b2-actin images in which figure? , 
 Why is this paper using U373 and U251? According to the ATCC, they are the same: https: www.lgcstandards-atcc.org Global FAQs C F U373_MG_ATCC_HTB17-1055.aspx?geo_country=fr There is not enough information given in the publication about the origins of the cells. Surely in 2019, the fact that these cells are not reliable models should be known, this is a very elementary mistake. ,