Melatonin protects against oxidative ER stress through the upregulation of PrPC. A, Western blot of p‐PERK, PERK, p‐eIF2α, eIF2α and ATF4 after treatment of melatonin‐pretreated MSCs with hydrogen peroxide (200 μmol/L). B, The levels of p‐PERK, p‐eIF2α and ATF4 were normalized to those of PERK, eIF2α and β‐actin, respectively. Values represent the mean ± SEM. *P < 0.05; **P < 0.01 vs untreated MSCs, ##
P < 0.01 vs MSCs treated with H2O2, $$
P < 0.01 vs MSCs treated with melatonin, and &&
P < 0.01 vs MSCs treated with melatonin and si‐PRNP. C, Western blot of p‐IRE1α, IRE1α, p‐JNK, JNK, p‐p38, p38 and CHOP after treatment of melatonin‐pretreated MSCs with hydrogen peroxide (200 μmol/L). D, The levels of p‐IRE1α, p‐JNK, p‐p38 and CHOP were normalized to those of IRE1α, JNK, p38 and β‐actin, respectively. Values represent the mean ± SEM. *P < 0.05; **P < 0.01 vs untreated MSCs, ##
P < 0.01 vs MSCs treated with H2O2, $$
P < 0.01 vs MSCs treated with melatonin, and &&
P < 0.01 vs MSCs treated with melatonin and si‐PRNP. E, Western blot of p‐PERK, PERK, p‐eIF2α, eIF2α and ATF4 in ischaemic‐injured tissues 1 days after injection with PBS, MSCs (MSC), MSCs treated with melatonin (MSC + Melatonin), MSCs treated with melatonin and PRNP siRNA (MSC + si‐PRNP + Melatonin), or MSCs treated with melatonin and scrambled siRNA (MSC + si‐Scr + Melatonin) in a murine hindlimb ischaemia model. F, The expressions of p‐PERK, p‐eIF2α and ATF4 were normalized to those of PERK, eIF2α, and α‐tubulin, respectively. Values represent the mean ± SEM. *P < 0.05; **P < 0.01 vs normal, ##
P < 0.01 vs PBS, $
P < 0.05; $$
P < 0.01 vs MSC, and &&
P < 0.01 vs MSC + si‐PRNP + Melatonin. G, Western blot of p‐IRE1α, IRE1α, p‐JNK, JNK, p‐p38, p38 and CHOP in the same tissues as in E. H, The expression levels of p‐IRE1α, p‐JNK, p‐p38 and CHOP were normalized to those of IRE1α, JNK, p38 and α‐tubulin, respectively. Values represent the mean ± SEM. *P < 0.05; **P < 0.01 vs normal, #
P < 0.05; ##
P < 0.01 vs PBS, $
P < 0.05; $$
P < 0.01 vs MSC, and &&
P < 0.01 vs MSC + si‐PRNP + Melatonin