AUTHOR=Li Hua , Kittur Farooqahmed S. , Hung Chiu-Yueh , Li P. Andy , Ge Xinghong , Sane David C. , Xie Jiahua 

TITLE=Quantitative Proteomics Reveals the Beneficial Effects of Low Glucose on Neuronal Cell Survival in an in vitro Ischemic Penumbral Model

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 14 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2020.00272

DOI=10.3389/fncel.2020.00272

ISSN=1662-5102

ABSTRACT=Understanding proteomic changes in the ischemic penumbra is crucial to rescue those salvageable cells and reduce the damage of ischemic stroke. Since the penumbra region is dynamic with heterogeneous cells/tissues, tissue sampling from animal models of stroke for molecular study is a challenge. In this study, cultured hippocampal cells under hypoxia treatment for 17.5 h with 0.69 mM low glucose (H+LG) could mimic ischemic penumbral cells since they had much higher cell viability and viable cell number compared to hypoxia without glucose (H-G) treatment. To validate established cell-based ischemic penumbral model and understand the beneficial effects of low glucose (LG), quantitative proteomics analysis was performed on H+LG, H-G, and normoxia with normal 22 mM glucose (N+G) treated cells. We identified 459 differentially abundant proteins (DAPs) between H-G and N+G, and further identified 115 DAPs between H+LG and H-G. Analysis of 115 DAPs revealed that LG promotes cell survival by activating HIF1α to enhance glycolysis; preventing the dysregulations of extracellular matrix remodeling, cell cycle and division, and antioxidant and detoxification; as well as attenuating inflammatory reaction response, protein synthesis and neurotransmission activity. Our results demonstrated that this established cell-based system closely mimics penumbral conditions and can be used for molecular studies.