During mitogen-induced transformation of human lymphocytes, phosphoglycerate kinase (PGK) exhibits new electrophoretic forms (pl=8.5-8.9). Electrophoresis and electrofocusing showed that the new forms are not due to expression of the autosomally linked isozyme found in semen (PGK-B; pl=9.7). The multiple electrophoretic forms are the result of protease modification of sex-linked PGK-A isozyme.When peripheral lymphocytes from young persons are stimulated in vitro with phytohemagglutinin, a selective increase in the levels of the glycolytic enzymes occurs concomitantly with blastogenesis. Human lymphocytes from a geriatric population were also subjected to mitogen stimulation. The initial levels of the enzymes were essentially identical in lymphocytes from young and old subjects as were mitogenfree cultured controls. However, during mitogen stimulation the cells from the old subjects failed to increase the glycolytic enzymes. This inability to activate glycolysis may be related to the decline in cell-mediated immunity which occurs with advancing age. Triosephosphate isomerase (TPI) has an increased thermolabile component in skin fibroblasts from patients with progeria (41.4 per cent)and Werner's syndrome (20.1 per cent) when compared with normal fibroblasts (0-3 per cent). The incorporation of various protease inhibitors failed to affect the percentages of heat-labile triosephosphate isomerases. The labile component appears to be identical to the deamidated form of the enzyme which accumulates in other aging cells. Isoelectric focusing demonstrated increased quantities of the deamidated TPI-A form in progeria and Werner's syndrome fibroblasts as compared to normal. The deamidated TPI-A was considerably more labile than the native TPI-B indicating the increased lability of triosephosphate isomerase in premature aging syndrome fibroblasts is due to an accumulation of the deamidated form of the enzyme. The levels of several proteases were found to be diminished in progeria fibroblast extracts as compared to normal. A deamidation mechanism of enzyme degradation plays a key role in the normal cellular catabolism of this enzyme and the mechanism for accumulation of defective forms in aging cells is apparently exacerbated by an impaired proteolytic capacity.
| Identifer | oai:union.ndltd.org:unt.edu/info:ark/67531/metadc331666 |
| Date | 08 1900 |
| Creators | Tollefsbol, Trygve O. |
| Contributors | Gracy, Robert W., Harris, Ben G., Norton, S. J., Lacko, Andras G., Jacobson, Elaine |
| Publisher | North Texas State University |
| Source Sets | University of North Texas |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
| Format | vi, 85 leaves : ill., Text |
| Rights | Public, Tollefsbol, Trygve O., Copyright, Copyright is held by the author, unless otherwise noted. All rights reserved. |
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