Suppression of Calcium-Dependent Membrane Currents in Human Fibroblasts by Replicative Senescence and Forced Expression of a Gene Sequence Encoding a Putative Calcium-Binding Protein

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 6; pp. 2186 - 2190
• Main Authors: Liu, Shi, Thweatt, Ray, Lumpkin, Charles K., Goldstein, Samuel
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15-03-1994; National Acad Sciences; National Academy of Sciences
• Subjects: Biological and medical sciences; Calcium; Calcium - metabolism; calcium-binding protein; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cell membranes; Cells; Cells, Cultured; Cellular biology; Cellular Senescence; Complex syndromes; dependent; Diploidy; DNA; Electric current; Fibroblasts; Fibroblasts - cytology; Fibroblasts - physiology; gene expression; Gene Expression Regulation; Genes; Humans; Male; man; Medical genetics; Medical sciences; membrane currents; Membrane Potentials; Membranes; Messenger RNA; Microinjections; Middle Aged; Protein Biosynthesis; replication; RNA; senescence; suppression; Werner syndrome; Werner Syndrome - metabolism; Endocrinopathy; Human; Skin disease; Senescence; Calcium; Diseases of the osteoarticular system; Ionic current; Genetic disease; Binding protein; Eye disease; Intracellular; Werner syndrome; Complex syndrome; Fibroblast
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.6.2186

Human diploid fibroblasts (HDFs) possess Ca2+-dependent membrane currents. These currents were suppressed in late-passage normal (senescent) HDFs and prematurely senescent HDFs derived from a subject with Werner syndrome (WS), compared with early-passage normal (young) HDFs. When young HDFs were microinjected with mRNA transcribed in vitro from a cDNA (WS3-10) which encodes a protein bearing a putative Ca2+-binding site and whose endogenous gene is overexpressed in senescent and WS HDFs, membrane currents fell to levels present in senescent and WS HDFs. Thus, both replicative senescence and forced expression of the WS3-10 gene sequence lead to suppression of Ca2+-dependent membrane currents, which suggests that a causal connection exists between these two processes.