| First Author | Josekutty J | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 20 | Pages | 14372-14383 |
| PubMed ID | 23532846 | Mgi Jnum | J:338768 |
| Mgi Id | MGI:6830018 | Doi | 10.1074/jbc.M113.459602 |
| Citation | Josekutty J, et al. (2013) Microsomal triglyceride transfer protein inhibition induces endoplasmic reticulum stress and increases gene transcription via Ire1alpha/cJun to enhance plasma ALT/AST. J Biol Chem 288(20):14372-14383 |
| abstractText | Microsomal triglyceride transfer protein (MTP) is a target to reduce plasma lipids because of its indispensable role in triglyceride-rich lipoprotein biosynthesis. MTP inhibition in Western diet fed mice decreased plasma triglycerides/cholesterol, whereas increasing plasma alanine/aspartate aminotransferases (ALT/AST) and hepatic triglycerides/free cholesterol. Free cholesterol accumulated in the endoplasmic reticulum (ER) and mitochondria resulting in ER and oxidative stresses. Mechanistic studies revealed that MTP inhibition increased transcription of the GPT/GOT1 genes through up-regulation of the IRE1alpha/cJun pathway leading to increased synthesis and release of ALT1/AST1. Thus, transcriptional up-regulation of GPT/GOT1 genes is a major mechanism, in response to ER stress, elevating plasma transaminases. Increases in plasma and tissue transaminases might represent a normal response to stress for survival. |
