Type

Journal Article

Authors

Noel G McElvaney
Shane J O'Neill
Clifford C Taggart
Alan Mulgrew
Catherine M Greene
Matthew W Lawless

Subjects

Biochemistry

Topics
interleukin 6 eukaryotic initiation factor 2 phosphorylation physiology molecular chaperones alpha 1 antitrypsin cricetinae carrier proteins protein conformation mutagenesis site directed animals nf kappa b transfection alpha 1 antitrypsin deficiency cell line heat shock proteins molecular chaperone grp78 protein subunits metabolism humans endoplasmic reticulum genetics chemistry protein folding serpina1 protein human enzymology signal transduction interleukin 8 biosynthesis cho cells

Activation of endoplasmic reticulum-specific stress responses associated with the conformational disease Z alpha 1-antitrypsin deficiency. (2004)

Abstract Conformational diseases are a class of disorders associated with aberrant protein accumulation in tissues and cellular compartments. Z alpha1-antitrypsin (A1AT) deficiency is a genetic disease associated with accumulation of misfolded A1AT in the endoplasmic reticulum (ER) of hepatocytes. We sought to identify intracellular events involved in the molecular pathogenesis of Z A1AT-induced liver disease using an in vitro model system of Z A1AT ER accumulation. We investigated ER stress signals induced by Z A1AT and demonstrated that both the ER overload response and the unfolded protein response were activated by mutant Z A1AT, but not wild-type M A1AT. Interestingly, activation of the unfolded protein response pathway required an additional insult, whereas NF-kappa B activation, a hallmark of the ER overload response, was constitutive. These findings have important implications for the design of future therapeutics for Z A1AT liver disease and may also impact on drug design for other conformational diseases.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Shane J O'Neill, Clifford C Taggart, Alan Mulgrew, Catherine M Greene, Matthew W Lawless

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54
 
4
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150