Potential and limitations of cultivated fibroblasts in the study of senescence in animals. A review on the murine skin fibroblasts system

Gansen, Paulette Van; Lerberghe, Nadine Van

doi:10.1016/0167-4943(88)90021-0

Cited by 21 publications

(8 citation statements)

References 95 publications

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“…In this study, we established as a study model an in vitro aging system [Van Gansen and Van Lerberghe, 1988] consisting of young and aging fibroblasts exposed to a sublethal dose of UVA (9 J/cm 2 )…”

Section: Discussionmentioning

confidence: 99%

UV irradiation increases ROS production via PKCδ signaling in primary murine fibroblasts

Bossi

Gartsbein

Leitges

et al. 2008

J of Cellular Biochemistry

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Ultraviolet (UV) irradiation is a major environmental factor responsible for a high incidence of premature skin aging, referred to as photoaging, as well as skin cancer and melanoma. UVA irradiation represents 90% of the solar UV light reaching the earth's surface, and yet the mechanisms by which it exerts its biological effects are not clear. UVA penetrates into the skin tissue, reaching the basal layers of the active dividing cells and, therefore, the contribution of UVA to skin damage may be significant. The majority of UVA energy is absorbed by unidentified photosensitizers in the cells which are postulated to generate reactive oxygen species (ROS). It has been believed that both chronological aging and photoaging share the same molecular features and, as such, it is very common to utilize UV irradiation for induction of skin aging. To determine the involvement of protein kinase isoforms in chronological aging and photoaging, we utilized in vitro aging model systems of primary murine fibroblasts and primary fibroblasts isolated from PKC null mice. We show for the first time distinct involvement of PKC isoforms PKCdelta and PKCalpha in photoaging versus cellular senescence. While chronological aging is accompanied by overexpression and activation of PKCalpha, UV irradiation and ROS production are associated with photoaging accompanied by PKCdelta downregulation and nuclear translocation.

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Section: Discussionmentioning

confidence: 99%

UV irradiation increases ROS production via PKCδ signaling in primary murine fibroblasts

Bossi

Gartsbein

Leitges

et al. 2008

J of Cellular Biochemistry

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“…1 A). Primary dermal fibroblast cultures are asynchronous, suggesting that heterogeneity of anti-LMNA G608G staining reflected cellular age (19). Indeed, Western blot analysis indicated that the progerin product was increased in cultures at late PPDs (Fig.…”

Section: Mutant Lamin a G608g Accumulates Within The Nucleus In A Celmentioning

confidence: 99%

Hutchinson–Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody

McClintock

Gordon

Djabali

2006

Proc. Natl. Acad. Sci. U.S.A.

183

192

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Hutchinson-Gilford progeria syndrome (HGPS; Online Mendelian Inheritance in Man accession no. 176670) is a rare disorder that is characterized by segmental premature aging and death between 7 and 20 years of age from severe premature atherosclerosis. Mutations in the LMNA gene are responsible for this syndrome. Approximately 80% of HGPS cases are caused by a G608 (GGC3 GGT) mutation within exon 11 of LMNA, which elicits a deletion of 50 aa near the C terminus of prelamin A. In this article, we present evidence that the mutant lamin A (progerin) accumulates in the nucleus in a cellular age-dependent manner. In human HGPS fibroblast cultures, we observed, concomitantly to nuclear progerin accumulation, severe nuclear envelope deformations and invaginations preventable by farnesyltransferase inhibition. Nuclear alterations affect cell-cycle progression and cell migration and elicit premature senescence. Strikingly, skin biopsy sections from a subject with HGPS showed that the truncated lamin A accumulates primarily in the nuclei of vascular cells. This finding suggests that accumulation of progerin is directly involved in vascular disease in progeria.aging ͉ atherosclerosis H utchinson-Gilford progeria syndrome (HGPS) is a rare, fatal genetic disorder that is characterized by accelerated aging in children. The LMNA gene encoding the A-type lamins A and C is the causative gene of HGPS (1-3). Approximately 80% of HGPS cases carry the heterozygous silent point mutation G608G within exon 11 of LMNA (3). This mutation creates an abnormal splice donor site, which produces a truncated protein (progerin) lacking residues 607-656 of prelamin A but retaining the C-terminal CAAX box, a target for prenylation (1-3).The nuclear lamina is a scaffold, which provides structural and mechanical stability for the nuclear envelope (NE); it consists primarily of type V intermediate filament proteins (A-and B-type lamins) and many inner-nuclear membrane proteins (4-7). Lamins interact with heterochromatin and transcriptional regulators, suggesting their important role in the maintenance of chromatin organization and gene expression (8).At the NE periphery, lamin precursors undergo a series of posttranslational modifications. B-type lamins are permanently isoprenylated, whereas prelamin A loses its modification after incorporation into the lamina by lamin A-specific processing steps involving Zmpste24 endoprotease (9-11). Because the endoproteolytic cleavage site is lost in the truncated lamin A (progerin), it was predicted to be permanently prenylated (3). Direct and indirect analyses have recently confirmed that progerin retains the farnesyl group (12)(13)(14)(15).Previous studies of A-type lamin distribution in primary dermal fibroblasts from HGPS patients showed nuclear abnormalities in size and shape in a subpopulation of cells in culture (3,16,17). Farnesylated progerin appears to be responsible for the nuclear deformations because administration of farnesyltransferase inhibitors to the HGPS fibroblast cultures normalized the nucle...

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“…2A, B) and because Cisd2 has been demonstrated to be associated with mitochondrial dysfunction and degenerative disorders in aging mammals [7], we hypothesized that senescent somatic cells (MEFs) or senescent stem cells (iPSCs) would also exhibit notable abnormalities in mitochondrial function. Serial passages have been shown to induce cellular senescence [32]; therefore, we assessed and compared mitochondrial potentials (DCm) by JC-1 analysis [24] among cells with various Cisd2 genotypes (Cisd2 +/+ , Cisd2 +/-, and Cisd2 -/-) at passages 1 to 5, and we investigated whether Cisd2 deficiency impairs the mitochondrial membrane potential in somatic cells or stem cells. In general, somatic cells (MEFs) with any given genotype exhibited a higher mitochondrial membrane potential.…”

Section: Cisd2 Regulates the Membrane Potential Of Ipscsmentioning

confidence: 99%

Dysregulation of Mitochondrial Functions and Osteogenic Differentiation in Cisd2-Deficient Murine Induced Pluripotent Stem Cells

Tsai¹,

Chien

Chuang

et al. 2015

Stem Cells and Development

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Potential and limitations of cultivated fibroblasts in the study of senescence in animals. A review on the murine skin fibroblasts system

Cited by 21 publications

References 95 publications

UV irradiation increases ROS production via PKCδ signaling in primary murine fibroblasts

UV irradiation increases ROS production via PKCδ signaling in primary murine fibroblasts

Hutchinson–Gilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody

Dysregulation of Mitochondrial Functions and Osteogenic Differentiation in Cisd2-Deficient Murine Induced Pluripotent Stem Cells

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