title: Time-dependent homeostasis between glucose uptake and consumption in astrocytes exposed to CoCl₂ treatment.
abstract: Hypoxia has been implicated in the pathology of the central nervous system during stroke. It also has a significant effect on the regulation of glucose transporters (GLUTs), and homeostasis between glucose uptake and consumption. CoCl2 is a hypoxia‑mimetic agent, and thus stabilizes the hypoxia‑inducible factor 1α (HIF‑1α) subunit and regulates GLUT genes. GLUT‑1 and GLUT‑3 are the most common isoforms of the GLUT family present in the brain, with the former primarily expressed in astrocytes and the latter in neurons under physiological conditions. However, it remains controversial whether GLUT‑3 is expressed in astrocytes. Additionally, it is unclear whether the regulation of GLUT‑1 and GLUT‑3, and glucose homeostasis, are affected by CoCl2 treatment in a time‑dependent manner. In the present study, mRNA and protein levels of GLUT‑1, GLUT‑3 and HIF‑1α in astrocytes were examined by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. The intracellular glucose concentration, glycogen storage, ATP content, pyruvate concentration, lactate dehydrogenase (LDH) release activity and cell viability in astrocytes were also investigated. The observations of the current study confirmed that both protein and mRNA levels of GLUT‑1 and GLUT‑3 were elevated in a time‑dependent manner induced by CoCl2 treatment, followed by accumulation of HIF‑1α. Furthermore, in the early period of CoCl2 treatment (≤8 h at 100 µM), LDH release, ATP content, glycogen storage and cell viability remained unchanged, whereas intracellular pyruvate concentration increased and glucose concentration was reduced. However, in the later period of CoCl2 treatment (>8 h at 100 µM), LDH release and intracellular pyruvate concentration increased, while intracellular glucose concentration, ATP content and glycogen storage were reduced. This may be due to disruption of homeostasis and reduced cell viability. In conclusion, alteration in the expression levels of GLUT‑1 and GLUT‑3, and the homeostasis between glucose uptake and consumption were affected by CoCl2 treatment, in a time‑dependent manner, and may result in reduced energy production and cell viability in astrocytes.
authors: Department of Basic Medicine, Nursing College, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Peng
authors: P
authors: Wang
authors: Department of Palliative Care and Hospice Care, The Ninth People's Hospital of Zhengzhou, Zhengzhou, Henan 450053, P.R. China.
authors: Ling
authors: L
authors: Li
authors: Department of Basic Medicine, Nursing College, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Zhenxiang
authors: Z
authors: Zhang
authors: Department of Infectious Disease, Clinical Pharmacology Base, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Quancheng
authors: Q
authors: Kan
authors: Department of Basic Medicine, Nursing College, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Suyan
authors: S
authors: Chen
authors: Department of Neuroimmunology, Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors: Feng
authors: F
authors: Gao
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006706:Homeostasis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008807:Mice, Inbred BALB C; D019289:Pyruvic Acid / Q000378:metabolism; D020521:Stroke / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse; D003035:Cobalt; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen; C018021:cobaltous chloride; D005947:Glucose