Differential effects of 24-hydroxycholesterol and 27-hydroxycholesterol on β-amyloid precursor protein levels and processing in human neuroblastoma SH-SY5Y cells

<p>Abstract</p> <p>Background</p> <p>Activation of the liver × receptors (LXRs) by exogenous ligands stimulates the degradation of β-amyloid 1–42 (Aβ42), a peptide that plays a central role in the pathogenesis of Alzheimer's disease (AD). The oxidized cholesterol products (oxysterols), 24-hydroxycholesterol (24-OHC) and 27-hydroxycholesterol (27-OHC), are endogenous activators of LXRs. However, the mechanisms by which these oxysterols may modulate Aβ42 levels are not well known.</p> <p>Results</p> <p>We determined the effect of 24-OHC and/or 27-OHC on Aβ generation in SH-SY5Y cells. We found that while 27-OHC increases levels of Aβ42, 24-OHC did not affect levels of this peptide. Increased Aβ42 levels with 27-OHC are associated with increased levels of β-amyloid precursor protein (APP) as well as β-secretase (BACE1), the enzyme that cleaves APP to yield Aβ. Unchanged Aβ42 levels with 24-OHC are associated with increased levels of sAPPα, suggesting that 24-OHC favors the processing of APP to the non-amyloidogenic pathway. Interestingly, 24-OHC, but not 27-OHC, increases levels of the ATP-binding cassette transporters, ABCA1 and ABCG1, which regulate cholesterol transport within and between cells.</p> <p>Conclusion</p> <p>These results suggest that cholesterol metabolites are linked to Aβ42 production. 24-OHC may favor the non-amyloidogenic pathway and 27-OHC may enhance production of Aβ42 by upregulating APP and BACE1. Regulation of 24-OHC: 27-OHC ratio could be an important strategy in controlling Aβ42 levels in AD.</p

BVRI Light Curves for 29 Type Ia Supernovae

BVRI light curves are presented for 27 Type Ia supernovae discovered during the course of the Calan/Tololo Survey and for two other SNe Ia observed during the same period. Estimates of the maximum light magnitudes in the B, V, and I bands and the initial decline rate parameter m15(B) are also given.Comment: 17 pages, figures and tables are not included (contact first author if needed), to appear in the Astronomical Journa

Foraging behavior in the Eastern Chipmunk Tamias striatus in northern Michigan.

We investigated foraging behavior in the Eastern chipmunk Tamias striatus. We predicted that females would forage more frequently, and earlier in the day than males. We found trends which showed that females do forage more often than males. However, our results showed that males tend to forage in the morning while females prefer foraging in the afternoon and evening. None of these observed trends proved statistically significant. We also predicted that chipmunks would prefer to forage in forested areas over open areas in order to avoid predators. This preference was not indicated by our results. Observational data indicated that intra-specific competition may be an important factor influencing chipmunk behavior. Possible explanations for these results have been offered.http://deepblue.lib.umich.edu/bitstream/2027.42/54711/1/3152.pdfDescription of 3152.pdf : Access restricted to on-site users at the U-M Biological Station