Figure 7

Glutamine induces apoptosis and arrests autophagy via the UPR in glucose-deprived conditions. A, Significantly higher levels of apoptosis were seen in LCC9 compared with LCC1 cells following treatment with 2 or 4 mM glutamine at 48 h. ANOVA, p < 0.05; *p < 0.05 for LCC9 versus LCC1 for indicated treatment. B, Time-course, 0, 24 and 48 h, analysis of the autophagosome-associated proteins LC3II (marker for autophagosome formation or enlargement) and p62/SQSTM1 (marker for autophagosome activity, degradation of cargo). Increased formation of autophagosomes but arrested cargo degradation was seen within 24 h in both LCC1 and LCC9 cells in glutamine only media (and in no-glucose + no glutamine) conditions at 24 and 48 h but not in glucose-only (or in glucose + glutamine) media. C, In presence of 2 or 4 mM glutamine at 48 h, LCC9 cells showed increased levels of MYC and MAX and LC3II but no change in SQSTM1/p62. D, Cellular levels of total reactive species (RS) was significantly elevated in LCC9 compared to LCC1 cells in incomplete media (ANOVA, p < 0.001; *p < 0.05 for LCC9 versus LCC1 with no glucose + no glutamine).