Preventive carnosine supplementation attenuates painful diabetic neuropathy via restoring mitochondrial function and suppressing inflammasome activation

Figure 7 dynamin-related protein 1 knockdown inhibits high glucose-induced NOD-like receptor pyrin domain-containing protein 3 inflammasome activation, whereas dynamin-related protein 1 overexpression attenuates the inhibitory effect of carnosine in PC12 cells. For Figure 7A-F, ^bP < 0.01 vs the control group; ^cP < 0.001 vs the control group; ^dP < 0.05 vs the high-glucose (HG) group; ^fP < 0.001 vs the HG group. For panels H-O, ^gP < 0.05 vs the vector control group, ^hP < 0.01 compared with the vector control group, ⁱP < 0.001 vs the vector control group; ^jP < 0.05 vs the vector HG group, ^kP < 0.01 vs the vector HG group, ^lP < 0.001 vs the vector HG group; ^mP < 0.01 vs vector carnosine group, ⁿP < 0.001 vs vector carnosine group. One-way analysis of variance with Tukey’s multiple comparisons test for Figure 7B-F, H, J-O. For Figure 7A-F, I-O, n = 4, G-H, n = 5. A-E: Western blotting of mitochondrial fission and NOD-like receptor pyrin domain-containing protein 3 inflammasome activation-related protein expression following lentivirus-short hairpin RNA targeting dynamin-related protein 1 knockdown, including representative electrophoresis bands and relative expression levels; F: Enzyme-linked immunosorbent assay showing interleukin-1β expression level; G: Representative fluorescence images of JC-1 monomers/aggregates in PC12 cells. Scale bar = 20 μm; H: Mitochondrial membrane potential level in PC12 cells; I-N: Western blotting of mitochondrial fission and NOD-like receptor pyrin domain-containing protein 3 inflammasome activation-related protein expression after lentivirus-dynamin-related protein 1 overexpression, including representative electrophoresis bands and relative expression levels; O: Enzyme-li O: Enzyme-linked immunosorbent assay indicating interleukin-1β expression level in PC12 cells. NLRP3: NOD-like receptor pyrin domain-containing protein 3; Drp1: Dynamin-related protein 1; HG: High-glucose; IL-1β: Interleukin-1β; LV-shDrp1: Lentivirus-short hairpin RNA targeting dynamin-related protein 1.