To elucidate the molecular mechanisms underlying the development of diabetic neuropathy, we isolated the Schwann cells from the sciatic nerves of adult rats and characterized the polyol pathway activity. Despite the presence of aldose reductase (AR) activity, no accumulation of sorbitol was observed
Regulation of Schwann cell proliferation in cultured segments of the adult rat sciatic nerve
✍ Scribed by Åsa Fex Svenningsen; Martin Kanje
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 178 KB
- Volume
- 52
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Schwann cell proliferation was studied in cultured segments of the rat sciatic nerve by measurement of [ 3 H] thymidine incorporation or through bromodeoxyuridine-(BrdU)-labelling and immunocytochemistry. The aim was to delineate mechanisms involved in the injury-induced proliferative response of Schwann cells. Removal of extracellular Ca 2؉ by addition of EGTA to the culture medium suppressed [ 3 H] thymidine incorporation as did the calmodulin inhibitor 48/80. The Ca 2؉ ionophore A23187 increased incorporation. Staurosporin, an inhibitor of protein kinase C (PKC), suppressed [ 3 H] thymidine incorporation while phorbol-12-myristate-13-acetate (PMA) enhanced incorporation. Manipulation of the cAMP system showed that increased cAMP levels inhibited proliferation. Inhibition of protein kinase A by HA 1004 increased the incorporation of [ 3 H] thymidine. Immunostaining for BrdU and glial specific markers together with morphological evaluation of myelin association showed that proliferation occurred in Schwann cells. The results are consistent with a model in which Schwann cell proliferation is enhanced by Ca 2؉ through activation of calmodulin-dependent and/or PKCdependent mechanisms. Inhibition is achieved through the cAMP system. Together, these results show that Schwann cells regulate proliferation differently in an integrated environment, e.g. the nerve structure, than in isolation as primary monocultures.
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