Alterations in the growth and protein content of human neuroblastoma cells in vitro induced by thyroid hormones, stress and ageing.
The effects of the thyroid hormone triiodothyronine (T3), nerve growth factor (NGF) and stress (exposure to heat or aluminum sulfate) on growth, development and ageing of human neuroblastoma cells were studied in vitro. Differentiation of cells using retinoic acid and NGF inhibits cell growth and proliferation; simultaneously, it promotes acquisition of neuronal phenotype, down-regulation of T3 receptors, and an increase in catecholaminergic tyrosine hydroxylase activity and microtubule assembly. The actions of T3 on neuronal differentiation resemble those of NGF and suggest the existence of NGF-T3 interactions. Exposure to stress inhibits cell growth and proliferation, increases immunoreactivity to the microtubule-assembling protein tau (which occurs in paired filaments of neurofibrillary tangles in the aged human brain), and facilitates formation of tau-ubiquitin complexes (which also occur in the aged brain). Stress does not prevent the inhibition of cell proliferation by high doses of T3; however, T3 doses that are equivalent to physiological levels reduce stress-induced inhibition of growth. Previous studies have shown that stress may also induce in these cells facsimile lesions of normal and abnormal ageing, such as accumulation of lipofuscin pigments, formation of paired helical filaments and increased immunoreactivity to tau, beta-amyloid proteins, and ubiquitin. These lesions may represent cellular and molecular manifestations of increased vulnerability and susceptibility to genetic and extrinsic factors (e.g. hormones and environmental influences) with ageing. It is proposed that neuroblastoma cells may serve as a model to study mechanisms of neuronal ageing and to identify agents and conditions capable of preventing, delaying or reducing metabolic abnormalities leading to age-associated disorders.
Isaeff
M
M
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Goya
L
L
Timiras
P S
PS
D000375:Aging / Q000502:physiology; D000534:Alum Compounds / Q000009:adverse effects*; D001921:Brain / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D008959:Models, Neurological; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009447:Neuroblastoma / Q000378:metabolism / Q000503:physiopathology*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D000534:Alum Compounds; D004273:DNA, Neoplasm; D009414:Nerve Growth Factors; D011988:Receptors, Thyroid Hormone; D014452:Ubiquitins; D016875:tau Proteins; D014284:Triiodothyronine; C041524:aluminum sulfate; D014212:Tretinoin