👤 Amanda C Doran

Activity of SERCA (sarco/endoplasmic reticulum Ca In vivo [U- CDN1163 increased cardiac ATPase activity, decreased cytosolic Ca SERCA activation promotes flux from nonglucose substrates to fuel cardiac mitochondrial metabolism in obese mice. Show less

Mutations that cause reduced expression of the full-length Survival Motor Neurons (SMN) protein are a major cause of spinal muscular atrophy (SMA), a disease characterized by degeneration of the alpha-motor neurons in the anterior horn of the spinal cord. The severity of SMA may be influenced by the actions of modifier genes. One potential modifier gene is represented by ZPR1, which is down-regulated in patients with SMA and encodes a zinc finger protein that interacts with complexes formed by SMN. To test the functional significance of ZPR1 gene down-regulation, we examined a mouse model with targeted ablation of the Zpr1 gene. We report that ZPR1-deficient mice exhibit axonal pathology and neurodegeneration. These data identify ZPR1 deficiency as a contributing factor in neurodegenerative disorders. Show less

To investigate the metabolism of nascent HDLs, apoA1/phosphatidylcholine (apoA1/PC) discs were infused IV over 4 hours into 7 healthy men. Plasma total apoA1 and phospholipid (PL) concentrations increased during the infusions. The rise in plasma apoA1 was greatest in small prebeta-migrating particles not present in the infusate. Total HDL unesterified cholesterol (UC) also increased simultaneously. After stopping the infusion, the concentrations of apoA1, PL, HDL UC, and small prebeta HDLs decreased, whereas those of HDL cholesteryl ester (CE) and large alpha-migrating apoA1 containing HDLs increased. ApoB-containing lipoproteins became enriched in CEs. Addition of apoA1/PC discs to whole blood at 37 degrees C in vitro also generated small prebeta HDLs, but did not augment the transfer of UC from erythrocytes to plasma. We conclude that the disc infusions increased the intravascular production of small prebeta HDLs in vivo, and that this was associated with an increase in the efflux and esterification of UC derived from fixed tissues. The extent to which the increase in tissue cholesterol efflux was dependent on that in prebeta HDL production could not be determined. Infusion of discs also reduced the plasma apoB and apoA2 concentrations, and increased plasma triglycerides and apoC3. Thus, nascent HDL secretion may have a significant impact on prebeta HDL production, reverse cholesterol transport and lipoprotein metabolism in humans. Show less