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. 2020 Apr 30;14:88. doi: 10.3389/fncel.2020.00088

FIGURE 2.

FIGURE 2

DOR inhibition or MOR activation enhanced BACE1 activities in normal conditions, while DOR activation attenuated BACE1-mediated cleavage activities in Aβ1–42 injury. BACE1 activities were examined at 30 min and 48 h after the drug treatment (N = 3 in each group). C: control. C + U: DOR was activated by UFP-512. C + U + N: PC12 cells were treated with UFP-512 plus naltrindole at the same time under normal conditions. C + N: DOR was inhibited by naltrindole. A: PC12 cells were treated with 20 μM Aβ1–42 oligomer to mimic the AD injury. A + U: DOR was activated by UFP-512 under AD injury. A + U + N: PC12 cells were treated with UFP-512 plus naltrindole together under AD injury. A + N: DOR was inhibited by naltrindole under AD injury. (A) DOR-mediated regulation of BACE1 activities in the physiological condition. *p < 0.05, **p<0.01 vs. (C). Note that 30-min treatment with DOR agonist UFP-512 significantly decreased BACE1 activities, whereas the application of DOR antagonist naltrindole enhanced BACE1 activities at both 30 min and 48 h after the treatment. (B) Effects of DADLE and DAMGO on BACE1 activity in normal conditions. *p < 0.05 vs. (C). Note that DADLE did not induce any significant change in BACE1 activity, while MOR agonist DAMGO significantly upregulated BACE1 activities. (C) Effects of DOR agonist UFP-512 and antagonist naltrindole on BACE1 activity under AD injury. The PC12 cells were treated with 20 μM Aβ1–42 oligomer for 48 h to mimic AD injury. UFP-512 and naltrindole were simultaneously or separately applied to these cells for 48 h or at the last 30 min of Aβ1–42 oligomer exposure. *p < 0.05, **p < 0.01 vs. (A). Note that DOR activation by UFP-512 significantly reduced BACE1 activities, whereas its inhibition with naltrindole reversed such effect. (D) Effects of MOR activation on BACE1 activity under AD injury. The cells with AD injury were exposed to DADLE or DAMGO at 1–5 μM. *p < 0.05, **p < 0.01 vs. (A). Note that the BACE1 cleavage activity was significantly reduced by DADLE at 1 μM after 48-h treatment, but largely enhanced by the application of DAMGO at 1 or 5 μM.