title: High concentrations of NaCl induce cell swelling leading to senescence in human cells.
abstract: Cell swelling and retardation in DNA replication are always observed in senescent cells. When DNA replication is slowed down with RNA and protein syntheses unchanged in proliferating cells, it causes a phenomenon known as unbalanced growth. The purpose of this study is to assess the role of cell swelling in unbalanced growth in terms of senescence and investigate the mechanism underlying this phenomenon. We tried to induce cell swelling with minimum damage to cells in this study. We perturbed the osmoregulatory functions to induce cell swelling under hypotonic and hypertonic conditions in normal human fibroblasts. Addition of excess NaCl was found to induce significant cell and nuclear swelling in dose- and time-dependent manners. Excess NaCl immediately retarded DNA replication, accumulated cells at G1 phase of the cell cycle, and eventually deprived division potential of the cells. Such cells showed typical senescent cell shape followed by expression of the typical senescence-associated genes. Excess NaCl also activated ERK1/2, p38, and JNK of the mitogen activated protein kinase family. Addition of U0126, an inhibitor of ERK1/2, prevented appearance of senescent features induced by excess NaCl. These results suggest that hypertonic conditions induce cell swelling due to unbalanced growth, thereby leading to cellular senescence.
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Yamakami
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan.
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Yonekura
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takauji
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan.|Ichiban Life Corporation, Yokohama, Kanagawa, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miki
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama, Kanagawa, 236-0027, Japan. dayusawa@yokohama-cu.ac.jp.|Ichiban Life Corporation, Yokohama, Kanagawa, Japan. dayusawa@yokohama-cu.ac.jp.
authors.forename: Dai
authors.initials: D
authors.lastname: Ayusawa
mesh_terms: D002461:Cell Line, Transformed; D016922:Cellular Senescence / Q000187:drug effects*; D006801:Humans; D012965:Sodium Chloride / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D012965:Sodium Chloride
keywords: Cell swelling; Cellular senescence; Hypertonic stress; Unbalanced growth