Unfolded protein response (upr) is not a mediator of apoptosis in peripheral blood mononuclear cells (PBMC) from Fabry disease patients

ROZENFELD P,; DEFRANCESCO PN; FOSSATI, CA

Hawai, EEUU

Congreso; 59th. Annual Meeting of the American Society of Human Genetics; 2009

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} p.MsoBodyText2, li.MsoBodyText2, div.MsoBodyText2 {margin-top:0cm; margin-right:0cm; margin-bottom:6.0pt; margin-left:0cm; line-height:200%; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-US; mso-fareast-language:EN-US;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> UNFOLDED PROTEIN RESPONSE (UPR) IS NOT A MEDIATOR OF APOPTOSIS IN PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) FROM FABRY DISEASE PATIENTS   ROZENFELD P, DE FRANCESCO N, FOSSATI C LISIN, Facultad de Ciencias Exactas, Universidad Nacional de La Plata. Argentina.   The pathophysiology of lysosomal storage diseases (LSD) is not well understood, and it is not solely explained by the burden of storage material. Increased apoptosis has been detected in different LSDs. ER stress/UPR was shown to be a common mediator of apoptosis both in neurodegenerative and non-neurodegenerative LSDs. However, a recent work in neuronopathic Gaucher disease could not demonstrate the involvement of UPR. The aim of this work is to analyze if ER stress/UPR is activated and related to apoptosis in PBMC from Fabry disease patients. We analyzed levels of caspases related to ER stress by western-blotting and expression of genes associated to UPR by quantitative PCR in PBMC from Fabry disease patients. We neither found differences in the levels of ER stress-related caspases, caspase 4 and caspase 12 nor changes in expression of genes CHOP, GADD34, BiP, XBP1, EDEM1, HSP90B1. We conclude that ER stress/UPR is not activated in PBMC from Fabry disease patients, and is not a mediator of apoptosis.   This work was supported by a research grant from Shire HGT.