Age-dependent reduction in sialidase activity of nuclear membranes from mouse brain.
Sialidase is an enzyme that cleaves alpha-linked sialic acid residues from sialoglycoconjugates and participates in various cellular functions. In the present study, we characterized sialidase activity in nuclear membranes from mouse brain and examined its age-related changes. A highly purified nuclear membrane preparation from 4-week-old mouse brain contained sialidase activity that hydrolyzed both 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid (4MU-Neu5Ac) and ganglioside GM3. The specific activities directed toward both substrates were 6.33+/-0.77 and 13.4+/-1.1pmol/mgprotein/min, respectively. Nuclear localization of sialidase activity was confirmed by fluorescent cytochemistry of intact nuclei using 5-bromo-4-chloro-3-indolyl-alpha-D-N-acetylneuraminic acid (X-Neu5Ac) as the substrate. Age-related changes in nuclear sialidase activity in brain tissue were investigated using mice of different ages (i.e. 2-week-, 4-week-, 14-month-, and 26-month-old). Sialidase activity toward 4MU-Neu5Ac had almost identical levels at 2nd and 4th weeks, but thereafter decreased rapidly; the activity at 26 months was about one third of the young levels. Sialidase activity toward GM3 also showed a similar developmental pattern, though the reduction at advancing ages was less than that of activity toward 4MU-Neu5Ac. The present study demonstrates that the activity of nuclear sialidase decreases with aging. The reduced activity of nuclear sialidase may be implicated with alterations of neural cell function during aging.
Saito
Megumi
M
Department of Clinical Pharmacology and Therapeutics, University of Shizuoka School of Pharmaceutical Sciences, 52-1 Yada, Japan. saitom@ys2.u-shizuoka-ken.ac.jp
Hagita
Hitoshi
H
Ito
Masaki
M
Ando
Susumu
S
Yu
Robert K
RK
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009439:Neuraminidase / Q000378:metabolism*; D009685:Nuclear Envelope / Q000201:enzymology*
D009439:Neuraminidase