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

Ming Shang Huang; Olugbenga Adebanjo; Baljit S. Moonga; Samuel Goldstein; F. Anthony Lai; David A. Lipschitz; Mone Zaidi

doi:10.1006/bbrc.1998.8392

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

Ming Shang Huang, Olugbenga Adebanjo, Baljit S. Moonga, Samuel Goldstein, F. Anthony Lai, David A. Lipschitz, Mone Zaidi

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 diphosphateribose (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.

Original language	English
Pages (from-to)	50-52
Number of pages	3
Journal	Biochemical and Biophysical Research Communications
Volume	245
Issue number	1
DOIs	https://doi.org/10.1006/bbrc.1998.8392
State	Published - 7 Apr 1998
Externally published	Yes

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title = "Upregulation of functional ryanodine receptors during in vitro aging of human diploid fibroblasts",

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 diphosphateribose (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.",

author = "Huang, {Ming Shang} and Olugbenga Adebanjo and Moonga, {Baljit S.} and Samuel Goldstein and Lai, {F. Anthony} and Lipschitz, {David A.} and Mone Zaidi",

note = "Funding Information: MZ acknowledges the National Institutes of Health (NIA, RO1 AG14917-02), Department of Veterans Affairs (Merit Review Award), and Amgen Corp. (San Diego, CA). The authors are grateful to Ms. E. Moerman for culturing HDFs, and to Professors MacIntyre, FRS, Cristofalo, PhD, and Manolagas, MD, PhD, for helpful discussion.",

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AU - Huang, Ming Shang

AU - Adebanjo, Olugbenga

AU - Moonga, Baljit S.

AU - Goldstein, Samuel

AU - Lai, F. Anthony

AU - Lipschitz, David A.

AU - Zaidi, Mone

N1 - Funding Information: MZ acknowledges the National Institutes of Health (NIA, RO1 AG14917-02), Department of Veterans Affairs (Merit Review Award), and Amgen Corp. (San Diego, CA). The authors are grateful to Ms. E. Moerman for culturing HDFs, and to Professors MacIntyre, FRS, Cristofalo, PhD, and Manolagas, MD, PhD, for helpful discussion.

PY - 1998/4/7

Y1 - 1998/4/7

N2 - 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 diphosphateribose (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.

AB - 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 diphosphateribose (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.

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

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