Life Sciences Commons^™

Chop Mediates Endoplasmic Reticulum Stress-Induced Apoptosis In Gimap5-Deficient T Cells, Steven Pino, Bryan O'Sullivan-Murphy, Erich Lidstone, Chaoxing Yang, Kathryn Lipson, Agata Jurczyk, Philip Diiorio, Michael Brehm, John Mordes, Dale Greiner, Aldo Rossini, Rita Bortell

Philip J diIorio Jr

Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis. We observed increases in ER stress-associated chaperones in T cells but not thymocytes or B cells from Gimap5(-/-) BBDP rats. We then …

Failure Of Alpha-Galactosylceramide To Prevent Diabetes In Virus-Inducible Models Of Type 1 Diabetes In The Rat, Prerna Chopra, Philip Diiorio, Steven Pino, S. Brian Wilson, Nancy Phillips, John Mordes, Aldo Rossini, Dale Greiner, Leonard Shultz, Rita Bortell

Philip J diIorio Jr

BACKGROUND: Alpha-galactosylceramide (alpha-GalCer) is an invariant natural killer T (iNKT) cell ligand that prevents type 1 diabetes in NOD mice. However, alpha-GalCer can activate or suppress immune responses, raising concern about its potential use in human diabetes.

MATERIALS AND METHODS: To evaluate this therapeutic issue further, BBDR and LEW.1WR1 rats were treated with Kilham rat virus (KRV) plus polyinosinic-polycytidylic acid, with or without alpha-GalCer, and followed for onset of diabetes.

RESULTS: alpha-GalCer did not prevent diabetes in inducible rat models. To investigate this discrepancy, we analyzed iNKT cell function. Splenocytes stimulated with alpha-GalCer produced similar levels of IFNgamma in all …

A Monomeric Protein In The Golgi Membrane Catalyzes Both N-Deacetylation And N-Sulfation Of Heparan Sulfate, Elisabet Mandon, Ellis Kempner, Masayuki Ishihara, Carlos Hirschberg

Elisabet Mandon

Recent studies have shown that the rat liver heparan sulfate N-deacetylase/N-sulfotransferase is a glycoprotein encoded by a single polypeptide chain of 882 amino acids. Using radiation inactivation analyses, we have now determined that in rat liver Golgi vesicles the target size for the N-deacetylase is 88 +/- 14 kDa, whereas that of the N-sulfotransferase is 92 +/- 8 kDa. These results, together with previous biochemical and molecular cloning approaches, demonstrate that 1) in rat liver Golgi membranes there exists only on population of molecules expressing both activities, 2) the active protein in the Golgi membrane functions as a monomer, and …