HIF-1α mediates energy metabolism of pancreatic exocrine cells after radiation

Objective: To study the radiation-induced mitochondrial damage and energy metabolic alteration in pancreatic exocrine cells, and to explore underlying mechanism. Methods: Rat pancreatic exocrine cells (AR42 J) were divided into control group and experimental group irradiated with 6 Gy of X-rays. Mitochondrial membrane potential was detected at 24, 48, 72 and 96 h, the lactic acid and ATP production were detected at 24 h and 48 h, and reactive oxygen species (ROS) were detected at 24 h after irradiation. The expressions of energy metabolism related factors of HIF-1α, LDHA and PDH were detected by Western blot. The animal experiments were conducted to confirm the changes. According to random number table, eight rats were randomly divided into two groups with 4 rats in each. The irradiated group was exposed to 12 Gy of X-rays, while the control group sham-irradiated. Results: Compared with the nonirradiated control group, the mitochondrial membrane potential (Δψm) of the experimental group was progressively decreased at 24-96 h after irradiation (t = 5.438-17.687, P < 0.05). The ATP content in the experimental group decreased at 24 h and 48 h (q = 17.300, 8.328, P < 0.05), the lactic acid increased (q = 21.790, 16.250, P < 0.05), and the ROS level increased (t = 7.935, P < 0.05). The expressions of HIF-1α and LDHA were significantly increased, but PDH was reduced after radiation. Silencing HIF-1α by siRNA eliminated radiation-induced energy metabolic alteration. These changes were confirmed with animal experiments by locally irradiating rats. Conclusions: The expression of HIF-1α is upregulated by irradiation, which leads to the change of energy metabolism as the enhancement of glycolysis pathway and the inhibition of aerobic oxidation of mitochondria in pancreatic exocrine cells. (authors)