Upregulation of functional ryanodine receptors during in vitro aging of human diploid fibroblasts

Biochemical and Biophysical Research Communications
M S HuangM Zaidi

Abstract

We demonstrate for the first time that cellular aging in vitro is accompanied by a dramatic elevation in the levels of ryanodine receptor-bearing Ca2+ channels. These channels normally reside within microsomal membranes and gate Ca2+ release from intracellular stores. We therefore measured cytosolic Ca2+ levels in 'young' (30 mean population doublings, MPDs) and 'senescent' (53 to 58 MPDs) human diploid fibroblasts (HDFs). Application of the known ryanodine receptor modulators, caffeine or cyclic adenosine diphosphate-ribose (cADPr), triggered cytosolic Ca2+ signals in both young and senescent cells. The signal magnitude however was significantly greater in senescent compared with young HDFs. In parallel, incubation with a highly specific anti-ryanodine receptor antiserum resulted in specific immunofluorescence only in senescent HDFs. We envisage that elevated levels of functional ryanodine receptors may underlie the defective Ca2+ handling and cellular degeneration that occurs with aging.

References

Jan 28, 1993·Nature·M J Berridge

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