Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1973 Sep;72(3):521–540.

Studies on Cellular Autophagocytosis

Cyclic AMP- and Dibutyryl Cyclic AMP-Stimulated Autophagy in Rat Liver

J D Shelburne, A U Arstila, B F Trump
PMCID: PMC1904032  PMID: 4125701

Abstract

Intraperitoneal injections of either cyclic AMP or dibutyryl cyclic AMP are capable of producing a wave of autophagy in rat liver which resembles closely that stimulated by glucagon. These autophagic vacuoles are acid-phosphatase-positive and appear to arise via the envelopment of organelles by double-walled cisterna. At later times these autophagic vacuoles are usually surrounded by a single membrane. Injection of equimolar amounts of 5′-AMP failed to produce a wave of autophagy. These findings constitute preliminary evidence that glucagon-stimulated autophagy is mediated at least in part by cyclic AMP.

Full text

PDF
521

Images in this article

537Fig 6
on p.537
538Fig 7
on p.538
538Fig 8
on p.538
538Fig 9
on p.538
538Fig 10
on p.538
539Fig 11
on p.539
539Fig 12
on p.539
539Fig 13
on p.539
539Fig 14
on p.539
535Fig 1
on p.535
535Fig 2
on p.535
535Fig 3
on p.535
535Fig 4
on p.535
536Fig 5
on p.536

Selected References

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

  1. ASHFORD T. P., BURDETTE W. J. RESPONSE OF THE ISOLATED PERFUSED HEPATIC PARENCHYMA TO HYPOXIA. Ann Surg. 1965 Aug;162:191–207. doi: 10.1097/00000658-196508000-00004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. ASHFORD T. P., PORTER K. R. Cytoplasmic components in hepatic cell lysosomes. J Cell Biol. 1962 Jan;12:198–202. doi: 10.1083/jcb.12.1.198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Altszuler N., Morrison A., Steele R., Bjerknes C. Metabolic effects of epinephrine, dibutyryl cyclic AMP, and glucagon infused intravenously into normal dogs. Ann N Y Acad Sci. 1971 Dec 30;185:101–107. doi: 10.1111/j.1749-6632.1971.tb45240.x. [DOI] [PubMed] [Google Scholar]
  4. Arstila A. U., Trump B. F. Studies on cellular autophagocytosis. The formation of autophagic vacuoles in the liver after glucagon administration. Am J Pathol. 1968 Nov;53(5):687–733. [PMC free article] [PubMed] [Google Scholar]
  5. BRANDES D., BUETOW D. E., BERTINI F., MALKOFF D. B. ROLE OF LYSOSOMES IN CELLULAR LYTIC PROCESSES. I. EFFECT OF CARBON STARVATION IN EUGLENA GRACILIS. Exp Mol Pathol. 1964 Dec;90:583–609. doi: 10.1016/0014-4800(64)90036-x. [DOI] [PubMed] [Google Scholar]
  6. Becker F. F., Cornwall C. C., Jr Phlorizin induced autophagocytosis during hepatocytic glycogenolysis. Exp Mol Pathol. 1971 Feb;14(1):103–109. doi: 10.1016/0014-4800(71)90056-6. [DOI] [PubMed] [Google Scholar]
  7. Bencosme S. A., Tsutsumi V. Fast method for processing biologic material for electron microscopy. Lab Invest. 1970 Oct;23(4):447–450. [PubMed] [Google Scholar]
  8. Butcher R. W., Robison G. A., Hardman J. G., Sutherland E. W. The role of cyclic AMP in hormone actions. Adv Enzyme Regul. 1968;6:357–389. doi: 10.1016/0065-2571(68)90023-x. [DOI] [PubMed] [Google Scholar]
  9. Chambers J. W., Georg R. H., Bass A. D. Effect of glucagon, cyclic 3',5'-adenosine monophosphate and its dibutyryl derivative on amino acid uptake by the isolated perfused rat liver. Endocrinology. 1970 Aug;87(2):366–370. doi: 10.1210/endo-87-2-366. [DOI] [PubMed] [Google Scholar]
  10. Deter R. L., Baudhuin P., De Duve C. Participation of lysosomes in cellular autophagy induced in rat liver by glucagon. J Cell Biol. 1967 Nov;35(2):C11–C16. doi: 10.1083/jcb.35.2.c11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Deter R. L., De Duve C. Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes. J Cell Biol. 1967 May;33(2):437–449. doi: 10.1083/jcb.33.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. ERICSSON J. L., TRUMP B. F., WEIBEL J. ELECTRON MICROSCOPIC STUDIES OF THE PROXIMAL TUBULE OF THE RAT KIDNEY. II. CYTOSEGRESOMES AND CYTOSOMES: THEIR RELATIONSHIP TO EACH OTHER AND TO THE LYSOSOME CONCEPT. Lab Invest. 1965 Jul;14:1341–1365. [PubMed] [Google Scholar]
  13. Ericsson J. L., Trump B. F. Observations on the application to electron microscopy on the lead phosphate technique for the demonstration of acid phosphatase. Histochemie. 1965 Mar 5;4(6):470–487. doi: 10.1007/BF00281900. [DOI] [PubMed] [Google Scholar]
  14. Exton J. H., Lewis S. B., Ho R. J., Robison G. A., Park C. R. The role of cyclic AMP in the interaction of glucagon and insulin in the control of liver metabolism. Ann N Y Acad Sci. 1971 Dec 30;185:85–100. doi: 10.1111/j.1749-6632.1971.tb45239.x. [DOI] [PubMed] [Google Scholar]
  15. Exton J. H., Mallette L. E., Jefferson L. S., Wong E. H., Friedmann N., Park C. R. Role of adenosine 3',5'-monophosphate in the control of gluconeogenesis. Am J Clin Nutr. 1970 Jul;23(7):993–1003. doi: 10.1093/ajcn/23.7.993. [DOI] [PubMed] [Google Scholar]
  16. Exton J. H., Park C. R. The role of cyclic AMP in the control of liver metabolism. Adv Enzyme Regul. 1968;6:391–407. doi: 10.1016/0065-2571(68)90024-1. [DOI] [PubMed] [Google Scholar]
  17. Exton J. H., Robison G. A., Sutherland E. W., Park C. R. Studies on the role of adenosine 3',5'-monophosphate in the hepatic actions of glucagon and catecholamines. J Biol Chem. 1971 Oct 25;246(20):6166–6177. [PubMed] [Google Scholar]
  18. FARQUHAR M. G., PALADE G. E. Junctional complexes in various epithelia. J Cell Biol. 1963 May;17:375–412. doi: 10.1083/jcb.17.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. HERDSON P. B., GARVIN P. J., JENNINGS R. B. FINE STRUCTURAL CHANGES PRODUCED IN RAT LIVER BY PARTIAL STARVATION. Am J Pathol. 1964 Aug;45:157–181. [PMC free article] [PubMed] [Google Scholar]
  20. HERS H. G. INBORN LYSOSOMAL DISEASES. Gastroenterology. 1965 May;48:625–633. [PubMed] [Google Scholar]
  21. Hardman J. G., Robison G. A., Sutherland E. W. Cyclic nucleotides. Annu Rev Physiol. 1971;33:311–336. doi: 10.1146/annurev.ph.33.030171.001523. [DOI] [PubMed] [Google Scholar]
  22. Kotoulas O. B., Phillips M. J. Fine structural aspects of the mobilization of hepatic glycogen. I. Acceleration of glycogen breakdown. Am J Pathol. 1971 Apr;63(1):1–22. [PMC free article] [PubMed] [Google Scholar]
  23. Lawrence A. M. Glucagon. Annu Rev Med. 1969;20:207–222. doi: 10.1146/annurev.me.20.020169.001231. [DOI] [PubMed] [Google Scholar]
  24. Levine R. A., Lewis S. E. Hepatic glycogenolytic activity of cyclic 3',5'-AMP and its monobutyryl derivative. Am J Physiol. 1967 Sep;213(3):768–770. doi: 10.1152/ajplegacy.1967.213.3.768. [DOI] [PubMed] [Google Scholar]
  25. Levine R. A., Lewis S. E., Shulman J., Washington A. Metabolism of cyclic adenosine 3',5'-monophosphate-8-14C by isolated, perfused rat liver. J Biol Chem. 1969 Aug 10;244(15):4017–4022. [PubMed] [Google Scholar]
  26. Liddle G. W., Hardman J. G. Cyclic adenosine monophosphate as a mediator of hormone action. N Engl J Med. 1971 Sep 2;285(10):560–566. doi: 10.1056/NEJM197109022851007. [DOI] [PubMed] [Google Scholar]
  27. Locke M., McMahon J. T. The origin and fate of microbodies in the fat body of an insect. J Cell Biol. 1971 Jan;48(1):61–78. doi: 10.1083/jcb.48.1.61. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. MILLER L. L. DIRECT ACTIONS OF INSULIN, GLUCAGON, AND EPINEPHRINE ON THE ISOLATED PERFUSED RAT LIVER. Fed Proc. 1965 May-Jun;24:737–744. [PubMed] [Google Scholar]
  29. Mallet L. E., Exton J. H., Park C. R. Control of gluconeogenesis from amino acids in the perfused rat liver. J Biol Chem. 1969 Oct 25;244(20):5713–5723. [PubMed] [Google Scholar]
  30. Menahan L. A., Wieland O. Interactions of glucagon and insulin on the metabolism of perfused livers from fasted rats. Eur J Biochem. 1969 May 1;9(1):55–62. doi: 10.1111/j.1432-1033.1969.tb00575.x. [DOI] [PubMed] [Google Scholar]
  31. OUDEA P. R. Anoxic changes of liver cells. Electron microscopic study after injection of colloidal mercury. Lab Invest. 1963 Mar;12:386–394. [PubMed] [Google Scholar]
  32. Pfeifer U. Celluläre Autophagie: Glykogensegregation im Frühstadium einer partiellen Leberatrophie. Virchows Arch B Cell Pathol. 1970;5(3):242–253. [PubMed] [Google Scholar]
  33. Pfeifer U. Tageszeitliche Rhythmik der zellulären Autophagie. Naturwissenschaften. 1971 Mar;58(3):152–152. [PubMed] [Google Scholar]
  34. Pohl S. L., Birnbaumer L., Rodbell M. Glucagon-sensitive adenyl cylase in plasma membrane of hepatic parenchymal cells. Science. 1969 May 2;164(3879):566–567. doi: 10.1126/science.164.3879.566. [DOI] [PubMed] [Google Scholar]
  35. Rosa F. Ultrastructural changes produced by glucagon, cyclic 3'5'-AMP and epinephrine on perfused rat livers. J Ultrastruct Res. 1971 Feb;34(3):205–213. doi: 10.1016/s0022-5320(71)80068-0. [DOI] [PubMed] [Google Scholar]
  36. Schofield B. H., Crossman I. W. Electron microscopy of hepatic cell lesions induced by electrocution. Arch Pathol. 1968 Aug;86(2):208–213. [PubMed] [Google Scholar]
  37. Scott D. F., Reynolds R. D., Pitot H. C., Potter V. R. Co-induction of the hepatic amino acid transport system and tyrosine aminotransferase by theophylline, glucagon and dibutyryl-cyclic AMP in vivo. Life Sci II. 1970 Oct 8;9(19):1133–1140. doi: 10.1016/0024-3205(70)90265-1. [DOI] [PubMed] [Google Scholar]
  38. Somlyo A. P., Somlyo A. V., Friedmann N. Cyclic adenosine monophosphate, cyclic guanosine monophosphate, and glucagon: effects on membrane potential and ion fluxes in the liver. Ann N Y Acad Sci. 1971 Dec 30;185:108–114. doi: 10.1111/j.1749-6632.1971.tb45241.x. [DOI] [PubMed] [Google Scholar]
  39. Sutherland E. W. On the biological role of cyclic AMP. JAMA. 1970 Nov 16;214(7):1281–1288. [PubMed] [Google Scholar]
  40. Swislocki N. I. Decomposition of dibutyryl cyclic AMP in aqueous buffers. Anal Biochem. 1970 Nov;38(1):260–269. doi: 10.1016/0003-2697(70)90175-2. [DOI] [PubMed] [Google Scholar]
  41. TRUMP B. F., SMUCKLER E. A., BENDITT E. P. A method for staining epoxy sections for light microscopy. J Ultrastruct Res. 1961 Aug;5:343–348. doi: 10.1016/s0022-5320(61)80011-7. [DOI] [PubMed] [Google Scholar]
  42. Tews J. K., Woodcock N. A., Harper A. E. Stimulation of amino acid transport in rat liver slices by epinephrine, glucagon, and adenosine 3',5'-monophosphate. J Biol Chem. 1970 Jun 10;245(11):3026–3032. [PubMed] [Google Scholar]
  43. Wicks W. D. Regulation of hepatic enzyme synthesis by cyclic AMP. Ann N Y Acad Sci. 1971 Dec 30;185:152–165. doi: 10.1111/j.1749-6632.1971.tb45245.x. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES