Journal
SCIENCE OF THE TOTAL ENVIRONMENT
Volume 836, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.scitotenv.2022.155691
Keywords
Arsenic; Metabolic reprogramming; HK2; AKT; ROS
Categories
Funding
- National Natural Science Foundation of China [81830099]
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Exposure to arsenic compounds poses a health risk to millions of people globally. Low-dose arsenic exposure induces aerobic glycolysis in cells, leading to aberrant proliferation. Accumulated ROS activates AKT and increases HK2 expression, determining the metabolic reprogramming.
Exposure to inorganic or organic arsenic compounds continues to pose substantial public health concerns for hundreds of millions of people around the globe. Highly exposed individuals are susceptible to various illnesses, including impairments and cancers of the lung, liver, skin and bladder. Long-term exposure to low-dose arsenic has been identified to induce aerobic glycolysis, which contributes to cells aberrant proliferation. However, the mechanism underlying arsenic-induced aerobic glycolysis is still unclear. Here, mtDNA copy number is enhanced in arsenic-exposed populations and a positive correlation between serum HK2 and urinary total arsenic was observed in the individuals with high urine arsenic (>= 0.032 mg/L). In a rat model of trivalent arsenic (iAs(3+)) exposure, the levels of HK2, NDUFA9 and NDUFB8 were increased in the rats treated with iAs(3+) daily by gavage for 12 weeks than those in the control rats. Subsequently, in a low-dose arsenic exposure cell model we found that 0.2 mu mol/L iAs3+ induced aerobic glycolysis to promote L-02 cells proliferation and inhibit apoptosis, in which HK2 played an important role. Further studies showed accumulated ROS determined the metabolic reprogramming via activating AKT and then increasing HK2 expression. On the one hand, activated AKT induced aerobic glycolysis by increasing HK2 to promote L-02 cells viability and DNA synthesis; on the other hand, phosphorylated AKT induced HK2 mitochondrial outer-membrane location with VDAC1 to inhibit apoptosis. Taken together, our results indicated that ROS induced by low-dose arsenic exposure determined energy metabolic reprogramming and acted a critical regulator for AKT-dependent HK2 expression and aerobic glycolysis.
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