Chinese Herbal Medicine Alleviates Myocardial Ischemia/Reperfusion Injury by Regulating Endoplasmic Reticulum Stress

Figure 1

UPR signaling pathway. With ER stress, GRP78 dissociates from three ER transmembrane sensors—IRE1, PERK, and ATF6—to allow their activation. Active IRE1 cleaves the mRNA encoding XBP1 to produce activated XBP1s, which enters the nucleus and induces the transcription of UPR target genes. Active PERK phosphorylates eIF2α to inhibit protein synthesis while upregulating ATF4 to active the UPR target genes. ATF4 also induces GADD34 to dephosphorylate eIF2α. ATF6 is hydrolyzed in the Golgi to produce an active fragment that enters into the nucleus to induce expression of UPR target genes.