Hsp90 participates in the necroptosis of mouse neural cells induced by aluminum through the RIP1/RIP3/MLKL pathway

Abstract

Objective: To investigate whether heat shock protein 90 (HSP90) participates in the necroptosis of C57BL/6 mouse neurons and spatial memory impairment induced by Aluminum maltol [Al (mal) (3)] through RIP1/RIP3/MLKL pathway. Methods: In March 2022, Thirty-two C57 mice were randomly divided into control group, Low dose group, a medium dose group, and a high-dose group, with 8 mice in each group, and injected intraperitoneally with physiological saline, 20, 40, and 80, respectivelyμmol/kgAl (mal) (3) was administered, it was injected 5 days a week and discontinued 2 days for 60 days. Morris water maze test was used to test the spatial learning and memory ability of mice. Nissl staining was used to observe the pathological changes of brain tissue. The protein expression levels of RIP1, RIP3, MLKL and HSP90 in hippocampus were determined by Western blotting. Results: In the water maze experiment, compared with the control group, the number of mice crossing the platform decreased in each dose group, the difference was statistically significant (H=9.50, P=0.023), and the number of mice crossing the platform was statistically significant among each dose group (P <0.05). Compared with the control group, the number of hippocampal nerve cells in each dose group decreased, the arrangement was disordered, and the Nissellite bodies decreased. Western blotting results showed that compared with the control group, the expression level of RIP1 protein in the hippocampus of mice in high-dose group was higher, and the difference was statistically significant (P <0.05). The expression levels of RIP3, MLKL and HSP90 in hippocampal tissue of mice in medium and high dose groups were increased, and the differences were statistically significant (P<0.05). After siRNA intervention decreased the expression of HSP90 protein, the expressions of HSP90, RIP1, RIP3 and MLKL in Al (mal) (3) groups were increased, and the differences were statistically significant (P<0.05) . Conclusion: Through RIP1/RIP3/MLKL pathway, HSP90 is involved in neuronal programmed necrosis and spatial memory impairment induced by maltol aluminum in C57 mice.