Cytoskeleton regulates β‐adrenergic hormonal stimulation in normal and leukemic white blood cells

Simantov, Rabi; Sachs, Leo

doi:10.1016/0014-5793(78)80300-7

Cited by 19 publications

(7 citation statements)

References 47 publications

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“…The colchicine analogue lumicolchicine, which does not disrupt microtubules, had no such effect (26,29). Although disruption of only other cytoskeletal components-microfilaments-by itself had no effect (19,26), the present results show that ad- dition of cytochalasin B in the presence of vinblastine or colchicine partially blocked the effect of the antitubulin compounds. Since the antitubulin drugs are presumably not competing for the same sites as cytochalasin B, it can be suggested that increase in cAMP synthesis by disruption of microtubules is partially dependent on unaltered activity of microfilaments after the change in the balance between these two major classes of cytoskeletal components.…”

Section: Differentialmentioning

confidence: 45%

“…We have studied the role of microtubules and microfilaments on the control of cell response to two specific hormones, (3-adrenergic and PGE1, in relation to the efficacy of cAMP formation and the ability of cells to terminate the hormone re- sponse and to develop desensitization. The present and previous results show that cAMP formation after stimulation of MGI+D+ cells (19) or normal leukocytes (19,26,29) with either of these two hormones is increased when the cells are treated with the antitubulin alkaloids colchicine and vinblastine sulfate. The colchicine analogue lumicolchicine, which does not disrupt microtubules, had no such effect (26,29).…”

Section: Differentialmentioning

confidence: 64%

“…These microtubule-disrupting compounds increased cAMP formation about 2-fold at the peak of the hormone effect 30 min after the addition of PGE1, and this effect was time dependent. However, the cells of MGI-D- (18,19) show that the response of myeloid leukemic cells to 3-adrenergic hormones and PGE1, hormones that are different chemically, is associated with the organization of cytoskeletal components. The following experiments were carried out to determine whether the cell nucleus participates in this development of desensitization to these hormones.…”

Section: Differentialmentioning

confidence: 99%

“…Mutant myeloid leukemic cells that were not so induced to differentiate (MGI-D-cells) (20,21) were unable to become desensitized to the same hormone, although they possess functional f-adrenergic receptors (18), did not show this sensitivity to antitubulin compounds (19). Therefore, the possibility that lack of desensitization reflects a general abnormality of cytoskeletal function that may also affect the cell response to other hormones was studied.…”

mentioning

confidence: 99%

“…Our previous study on the possible role of cytoskeleton compounds in the function of fl-adrenergic receptors has shown that normal peritoneal macrophages and myeloid leukemic cells that can be induced to differentiate normally to mature cells by the macrophage-and granulocyte-inducing protein MGI (MGI+D+ cells) that are desensitized after 3-adrenergic stimulation (18) were also sensitive, in their cAMP formation, to the microtubule-disrupting agents vinblastine sulfate and colchicine (19). Mutant myeloid leukemic cells that were not so induced to differentiate (MGI-D-cells) (20,21) were unable to become desensitized to the same hormone, although they possess functional f-adrenergic receptors (18), did not show this sensitivity to antitubulin compounds (19).…”

mentioning

confidence: 99%

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Desensitization of enucleated cells to hormones and role of cytoskeleton in control of normal hormonal response.

Simantov¹,

Shkolnik²,

Sachs³

1980

Proc. Natl. Acad. Sci. U.S.A.

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Prostaglandin E1 and the ,B-adrenergic hormone I-isoproterenol stimulated cyclic AMP formation in both nucleated and enucleated myeloid leukemic cells that could be induced to differentiate normally to mature cells by the macrophage-and granulocyte-inducing protein MGI (MGI+D+ cells). Enucleated as well as nucleated MGI+D+ cells also desensitized Results on the cellular effects of dibutyryl cyclic AMP (cAMP) and the process of reverse transformation have led to the hypothesis that cytoskeletal components regulate the transfer of information from the cell membrane to the nucleus and that disorganization of these structures can lead to abnormal cell behavior (1-4). Study of some surface receptor-mediated responses (5-7) has also shown that the activity of surface-bound cytoskeletal components can regulate the dynamics of surface receptors that may be required for information transfer from the cell membrane (5). The altered growth pattern in some cell types can be associated with changes in the receptor binding of compounds such as epidermal growth factor (8), insulin (9), or catecholamines (10). However, a crucial point also to be considered is that abnormal cell growth and differentiation may reflect lesions in postbinding events that control the initiation and termination of hormone response and hormone desensitization. Hormone-regulated cAMP formation by surface-bound adenylate cyclase is the result of an interaction between this enzyme and at least two other components, the hormone receptor and the guanyl nucleotide binding site (11)(12)(13)(14)(15)(16)(17) (18), did not show this sensitivity to antitubulin compounds (19). Therefore, the possibility that lack of desensitization reflects a general abnormality of cytoskeletal function that may also affect the cell response to other hormones was studied. The present studies include the use of enucleation to determine the extranuclear nature of hormone desensitization and the role of cytoskeletal structures in the control of hormone response in enucleated cells. MATERIALS AND METHODSThe leukemic cells used were clones of mouse myeloid leukemic cells isolated from a spontaneous or x-irradiation-induced myeloid leukemias as described (20). The cell clones 11 and 7-M18 were MGI+D+ and clones 1 and 6 were MGI-D-, based on their ability to be induced to differentiate in culture by the macrophage-and granulocyte-inducing protein MGI (20,21). Cells were cultured in Eagle's medium with a 4-fold increased concentration of amino acids and vitamins (H-21, GIBCO) and 10% inactivated fetal calf serum (18). Three or 4 days after seeding, the cells were collected, counted, and preincubated for 20 min at 107 cells per ml of culture medium containing 0.5 mM of the potent phosphodiesterase inhibitor RO-20-1724/1 (kindly donated by Hoffmann-La Roche) with or without 1 ,g of vinblastine sulfate (Ely Lilly), colchicine (Sigma), or cytochalasin B (Aldrich) per ml. Prostaglandin E1 (PGE1) (Sigma) was then added at the indicated concentration. Samples were collected before or...

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Section: Differentialmentioning

confidence: 45%