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However, prolonged activation of UPR leads to activation of JNK, glycogen synthase kinase 3 (GSK3), and transcription factor CCAAT/enhancer-binding homologous protein (CHOP), all of which upregulate pro-death proteins such as p53 up-regulation of apoptosis regulators (PUMA) and extrinsic pathways including tumor necrosis factor (TNF)-associated apoptosis-inducing ligands (TRAIL) to induce cell death through transcriptional upregulation of TRAIL receptor 2 (TRAIL-R2) expression

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For example, long-term use of oral contraceptives may lower levels of Vitamin B2 (riboflavin) , while some diabetes and epilepsy drugs affect Vitamin B12 (cobalamin) levels