The role of glycosidically bound mannose in the assimilation of [beta]-galactosidase by generalized gangliosidosis fibroblasts

Bovine testicular [beta]-galactosidase is rapidly assimilated by generalized gangliosidosis skin fibroblasts. The enzyme contains equimolar amounts of mannose and glucosamine and strongly binds to concanavalin A-Sepharose. Pretreatment of [beta]-galactosidase with a mannosidase preparation from reduced the rate of assimilation of the enzyme 97%. These data indicate that mannosyl residues play a role in assimilation of the enzyme. This conclusion is supported by observed inhibition of [beta]-galactosidase assimilation by mannose, methyl [alpha]- and [beta]-mannopyranosides, and mannose-containing testicular glycoproteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21625/1/0000004.pd

Biochemical Studies On Gm1 Gangliosidosis Type I Skin Fibroblasts.

PhDBiochemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/189133/2/7609475.pd

Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease

<div><p>Mitochondria-induced oxidative stress and flawed autophagy are common features of neurodegenerative and lysosomal storage diseases (LSDs). Although defective autophagy is particularly prominent in Pompe disease, mitochondrial function has escaped examination in this typical LSD. We have found multiple mitochondrial defects in mouse and human models of Pompe disease, a life-threatening cardiac and skeletal muscle myopathy: a profound dysregulation of Ca²⁺ homeostasis, mitochondrial Ca²⁺ overload, an increase in reactive oxygen species, a decrease in mitochondrial membrane potential, an increase in caspase-independent apoptosis, as well as a decreased oxygen consumption and ATP production of mitochondria. In addition, gene expression studies revealed a striking upregulation of the β 1 subunit of L-type Ca²⁺ channel in Pompe muscle cells. This study provides strong evidence that disturbance of Ca²⁺ homeostasis and mitochondrial abnormalities in Pompe disease represent early changes in a complex pathogenetic cascade leading from a deficiency of a single lysosomal enzyme to severe and hard-to-treat autophagic myopathy. Remarkably, L-type Ca²⁺channel blockers, commonly used to treat other maladies, reversed these defects, indicating that a similar approach can be beneficial to the plethora of lysosomal and neurodegenerative disorders.</p></div