Fig. 4: Exposure to hypoxia causes conversion of 26S proteasome to immunoproteasome in MSCs. | Cell Death & Disease

Fig. 4: Exposure to hypoxia causes conversion of 26S proteasome to immunoproteasome in MSCs.

From: Hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of mesenchymal stem cells

Fig. 4

Human bone marrow-derived MSCs were incubated in a hypoxia chamber for 24 h. a, b Co-immunoprecipitation analysis was performed in cell lysates to study binding between 19S and 20S subunits; as well as binding between 11S and 20S subunits. a The binding affinity between 19S proteasome (Sug1) and 20S proteasome α3 (PSMA4) decreased significantly in hypoxic MSCs compared to normoxic cells. b The binding between 11S subunit (PA28α) and α3 (PSMA4); as well as 11S subunit (PA28α) and α6 (PSMA1) increased in hypoxic MSCs vs. normoxic MSCs. c Proteasome degradation activities of 26S proteasome and immunoproteasome were measured using specific substrates for these two proteasomes: SUC-LLVY-AMC (specific for 26S proteolytic function), and Ac-PAL-AM as well as Ac-ANW-AMC (specific substrates for proteolytic activities of immunoproteasome subunits β1i/LMP2 and β5i/LMP7). There was significant decrease in 26S proteasome activity in hypoxic MSCs compared to normoxic MSCs. However, immunoproteasome activity significantly increased in hypoxic MSCs compared to normoxic cells; n = 5. *p < 0.05 compared to normoxic MSC. Each experiment was repeated 3–4 times.

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