Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1985 Aug 1;101(2):339–349. doi: 10.1083/jcb.101.2.339

Effects of swainsonine on rat liver and kidney: biochemical and morphological studies

PMCID: PMC2113680  PMID: 3926777

Abstract

Among the reported effects of the plant toxin swainsonine in animals are a decreased level of Golgi mannosidase II activity, an increase in lysosomal alpha-D-mannosidase activity, oligosaccharide accumulation, vacuolization of cells, and neurological changes. We now find that, in the rat, the alkaloid rapidly induces vacuolization of both liver and kidney cells, but oligosaccharides accumulate only in the latter. We demonstrate by enzyme- and immunocytochemistry that the induced pleomorphic vacuoles are lysosomal in nature. The vacuoles do not appear to be derived from the Golgi apparatus, which retains its typical ultrastructural appearance, but are formed by autophagy. In swainsonine-fed rats, the lysosomal system is highly developed in hepatocytes, Kupffer cells, and cells of the proximal convoluted tubules. The relation of this hypertrophy of the lysosomal system to the known effects of swainsonine on glycoprotein biosynthesis and on Golgi and lysosomal alpha-mannosidases is not clear. In addition, in liver there occurs a marked increase in mitotic figures in the hepatocytes. This occurred in the absence of both cell death and increased liver size as estimated by gross morphology.

Full Text

The Full Text of this article is available as a PDF (6.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burditt L. J., Chotai K., Hirani S., Nugent P. G., Winchester B. G., Blakemore W. F. Biochemical studies on a case of feline mannosidosis. Biochem J. 1980 Sep 1;189(3):467–473. doi: 10.1042/bj1890467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dorling P. R., Huxtable C. R., Vogel P. Lysosomal storage in Swainsona spp. toxicosis: an induced mannosidosis. Neuropathol Appl Neurobiol. 1978 Jul-Aug;4(4):285–295. doi: 10.1111/j.1365-2990.1978.tb00547.x. [DOI] [PubMed] [Google Scholar]
  3. FRIEND D. S., MURRAY M. J. OSMIUM IMPREGNATION OF THE GOLGI APPARATUS. Am J Anat. 1965 Jul;117:135–149. doi: 10.1002/aja.1001170109. [DOI] [PubMed] [Google Scholar]
  4. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  5. Jolly R. D. Mannosidosis of Angus Cattle: a prototype control program for some genetic diseases. Adv Vet Sci Comp Med. 1975;19:1–21. [PubMed] [Google Scholar]
  6. Matsuura F., Nunez H. A., Grabowski G. A., Sweeley C. C. Structural studies of urinary oligosaccharides from patients with mannosidosis. Arch Biochem Biophys. 1981 Apr 1;207(2):337–352. doi: 10.1016/0003-9861(81)90041-2. [DOI] [PubMed] [Google Scholar]
  7. Molyneux R. J., James L. F. Loco intoxication: indolizidine alkaloids of spotted locoweed (Astragalus lentiginosus). Science. 1982 Apr 9;216(4542):190–191. doi: 10.1126/science.6801763. [DOI] [PubMed] [Google Scholar]
  8. Novikoff A. B., Novikoff P. M. Cytochemical contributions to differentiating GERL from the Golgi apparatus. Histochem J. 1977 Sep;9(5):525–551. doi: 10.1007/BF01002901. [DOI] [PubMed] [Google Scholar]
  9. Novikoff P. M., La Russo N. F., Novikoff A. B., Stockert R. J., Yam A., Le Sage G. D. Immunocytochemical localization of lysosomal beta-galactosidase in rat liver. J Cell Biol. 1983 Nov;97(5 Pt 1):1559–1565. doi: 10.1083/jcb.97.5.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Novikoff P. M., Tulsiani D. R., Touster O., Yam A., Novikoff A. B. Immunocytochemical localization of alpha-D-mannosidase II in the Golgi apparatus of rat liver. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4364–4368. doi: 10.1073/pnas.80.14.4364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ockerman P. A. Mannosidosis: isolation of oligosaccharide storage material from brain. J Pediatr. 1969 Sep;75(3):360–365. doi: 10.1016/s0022-3476(69)80259-3. [DOI] [PubMed] [Google Scholar]
  12. Shoup V. A., Touster O. Purification and characterization of the alpha-D-mannosidase of rat liver cytosol. J Biol Chem. 1976 Jul 10;251(13):3845–3852. [PubMed] [Google Scholar]
  13. Tartakoff A. M., Vassalli P. Plasma cell immunoglobulin secretion: arrest is accompanied by alterations of the golgi complex. J Exp Med. 1977 Nov 1;146(5):1332–1345. doi: 10.1084/jem.146.5.1332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Tulsiani D. R., Broquist H. P., James L. F., Touster O. The similar effects of swainsonine and locoweed on tissue glycosidases and oligosaccharides of the pig indicate that the alkaloid is the principal toxin responsible for the induction of locoism. Arch Biochem Biophys. 1984 Jul;232(1):76–85. doi: 10.1016/0003-9861(84)90522-8. [DOI] [PubMed] [Google Scholar]
  15. Tulsiani D. R., Buschiazzo H. O., Tolbert B., Touster O. Changes in plasma hydrolase activities in hereditary and streptozotocin-induced diabetes. Arch Biochem Biophys. 1977 May;181(1):216–227. doi: 10.1016/0003-9861(77)90500-8. [DOI] [PubMed] [Google Scholar]
  16. Tulsiani D. R., Harris T. M., Touster O. Swainsonine inhibits the biosynthesis of complex glycoproteins by inhibition of Golgi mannosidase II. J Biol Chem. 1982 Jul 25;257(14):7936–7939. [PubMed] [Google Scholar]
  17. Tulsiani D. R., Hubbard S. C., Robbins P. W., Touster O. alpha-D-Mannosidases of rat liver Golgi membranes. Mannosidase II is the GlcNAcMAN5-cleaving enzyme in glycoprotein biosynthesis and mannosidases Ia and IB are the enzymes converting Man9 precursors to Man5 intermediates. J Biol Chem. 1982 Apr 10;257(7):3660–3668. [PubMed] [Google Scholar]
  18. Tulsiani D. R., Touster O. Swainsonine causes the production of hybrid glycoproteins by human skin fibroblasts and rat liver Golgi preparations. J Biol Chem. 1983 Jun 25;258(12):7578–7585. [PubMed] [Google Scholar]
  19. Tulsiani D. R., Touster O. Swainsonine, a potent mannosidase inhibitor, elevates rat liver and brain lysosomal alpha-D-mannosidase, decreases Golgi alpha-D-mannosidase II, and increases the plasma levels of several acid hydrolases. Arch Biochem Biophys. 1983 Jul 15;224(2):594–600. doi: 10.1016/0003-9861(83)90247-3. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES