Preventing and reversing the cellular consequences of Z alpha-1 antitrypsin accumulation by targeting s4A
S Alam, J Wang, S Janciauskiene, R Mahadeva - Journal of hepatology, 2012 - Elsevier
BACKGROUND & AIMS: The Z variant (Glu342Lys) of α1-antitrypsin (AT) polymerizes and
accumulates in the hepatocyte endoplasmic reticulum (ER) predisposing to neonatal
hepatitis and liver cirrhosis. The resultant secretory defect leaves the lungs vulnerable to
elastolysis and early-onset emphysema. Our aim in this study was to evaluate the effect of
targeting strand 4a (s4A) as a strategy to inhibit polymerization and restore plasma
secretion. METHODS: HEK293 cells and HepG2 cells were transfected with Z-AT (Z-AT …
accumulates in the hepatocyte endoplasmic reticulum (ER) predisposing to neonatal
hepatitis and liver cirrhosis. The resultant secretory defect leaves the lungs vulnerable to
elastolysis and early-onset emphysema. Our aim in this study was to evaluate the effect of
targeting strand 4a (s4A) as a strategy to inhibit polymerization and restore plasma
secretion. METHODS: HEK293 cells and HepG2 cells were transfected with Z-AT (Z-AT …