Aberrant Caspase Activation in Laminin-α2-Deficient Human Myogenic Cells is Mediated by p53 and Sirtuin Activity.

ABSTRACT: BACKGROUND:Mutations in the LAMA2 gene encoding laminin-α2 cause congenital muscular dystrophy Type 1A (MDC1A), a severe recessive disease with no effective treatment. Previous studies have shown that aberrant activation of caspases and cell death through a pathway regulated by BAX and KU70 is a significant contributor to pathogenesis in laminin-α2-deficiency. OBJECTIVES:To identify mechanisms of pathogenesis in MDC1A. METHODS:We used immunocytochemical and molecular studies of human myogenic cells and mouse muscles-comparing laminin-α2-deficient vs. healthy controls-to identify mechanisms that regulate pathological activation of caspase in laminin-α2-deficiency. RESULTS:In cultures of myogenic cells from MDC1A donors, p53 accumulated in a subset of nuclei and aberrant caspase activation w

SUBMITTER: Yoon S 

PROVIDER: S-EPMC5836413 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature