Insights into the Novel Hydrolytic Mechanism of a Diethyl 2-Phenyl-2-(2-arylacetoxy)methyl Malonate Ester-Based Microsomal Triglyceride Transfer Protein (MTP) Inhibitor

2012 ◽  
Vol 25 (10) ◽  
pp. 2138-2152 ◽  
Author(s):  
Tim Ryder ◽  
Gregory S. Walker ◽  
Theunis C. Goosen ◽  
Roger B. Ruggeri ◽  
Edward L. Conn ◽  
...  
Keyword(s):  
Microsomal Triglyceride Transfer Protein ◽  
The Novel ◽  
Transfer Protein ◽  
Methyl Malonate ◽  
Hydrolytic Mechanism

scholarly journals Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia

2000 ◽  
Vol 41 (8) ◽  
pp. 1199-1204 ◽  
Author(s):  
Ken Ohashi ◽  
Shun Ishibashi ◽  
Jun-ichi Osuga ◽  
Ryu-ichi Tozawa ◽  
Kenji Harada ◽  
...  
Keyword(s):  
Protein Gene ◽  
Microsomal Triglyceride Transfer Protein ◽  
Novel Mutations ◽  
Transfer Protein

Liver Microsomal Triglyceride Transfer Protein Is Involved in Hepatitis C Liver Steatosis

2006 ◽  
Vol 130 (6) ◽  
pp. 1661-1669 ◽  
Author(s):  
Silvia Mirandola ◽  
Stefano Realdon ◽  
Jahangir Iqbal ◽  
Martina Gerotto ◽  
Francesca Dal Pero ◽  
...  
Keyword(s):  
Hepatitis C ◽  
Liver Steatosis ◽  
Microsomal Triglyceride Transfer Protein ◽  
Transfer Protein

scholarly journals ApoB100 is required for increased VLDL-triglyceride secretion by microsomal triglyceride transfer protein inob/obmice

2008 ◽  
Vol 49 (9) ◽  
pp. 2013-2022 ◽  
Author(s):  
Zhouji Chen ◽  
Elizabeth P. Newberry ◽  
Jin Y. Norris ◽  
Yan Xie ◽  
Jianyang Luo ◽  
...  
Keyword(s):  
Microsomal Triglyceride Transfer Protein ◽  
Transfer Protein ◽  
Triglyceride Secretion ◽  
Vldl Triglyceride

scholarly journals Microsomal Triglyceride Transfer Protein Inhibition Induces Endoplasmic Reticulum Stress and Increases Gene Transcription via Ire1α/cJun to Enhance Plasma ALT/AST

2013 ◽  
Vol 288 (20) ◽  
pp. 14372-14383 ◽  
Author(s):  
Joby Josekutty ◽  
Jahangir Iqbal ◽  
Takao Iwawaki ◽  
Kenji Kohno ◽  
M. Mahmood Hussain
Keyword(s):  
Endoplasmic Reticulum ◽  
Free Cholesterol ◽  
Plasma Lipids ◽  
Microsomal Triglyceride Transfer Protein ◽  
Major Mechanism ◽  
Protein Inhibition ◽  
Transfer Protein ◽  
Oxidative Stresses ◽  
Triglyceride Rich Lipoprotein ◽  
Response To Stress

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 IRE1α/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.

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