Chronic in vivo exposure to glucocorticoids prolongs cellular lifespan: the case of Cushing's syndrome-patients' fibroblasts

Pratsinis, Harris; Tsagarakis, Stylianos; Zervolea, Irene; Giannakopoulos, F.; Stathakos, Dimitri; Thalassinos, N. C.; Kletsas, Dimitris

doi:10.1016/s0531-5565(02)00130-4

Cited by 20 publications

(24 citation statements)

References 44 publications

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“…All these changes are clearly in an opposite direction from the functional phenotype of CFs reported here. In this context, and in agreement with the data presented here, we have recently shown that CFs exhibited a remarkable extension of their in vitro lifespan (36).…”

Section: Discussionsupporting

confidence: 92%

The impact of chronic in vivo glucocorticoid excess on the functional characteristics of human skin fibroblasts obtained from patients with endogenous Cushing’s syndrome

Zervolea

Pratsinis²,

Tsagarakis³

et al. 2005

eur j endocrinol

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Objective: Chronic exposure to elevated glucocorticoid (GC) concentrations induces detrimental effects in several tissues. In the skin, GCs provoke intense alterations on various parameters of the physiology of fibroblasts, cumulatively leading to skin atrophy and impaired wound healing. As there are concerns that GCs may generate permanent adverse functional changes, we have investigated whether chronic in vivo exposure to GC excess results in persisting defects in skin fibroblasts. Design and methods: We have studied in vitro primary skin fibroblast cultures obtained from patients suffering from endogenous Cushing's syndrome (CF), as well as from sex-and age-matched normal donors (NF). The following functional parameters were investigated: cell proliferation, secretion of collagen, matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases; TIMPs) and contractile capacity. Results: CFs, grown under standard culture conditions in the absence of a hypercortisolemic milieu, exhibited an increased proliferative capacity and a higher final cell culture density compared with NFs. Collagen synthesis, in the absence or presence of transforming growth factor-b, was equal to that of NFs. However, CFs secreted comparatively lower levels of MMP-1, MMP-2 and TIMP-1, and nearly equal levels of TIMP-2. CFs also exhibited an increased ability to contract gels of polymerized collagen. Conclusions: Collectively, these functional characteristics of CFs are in contrast to the known catabolic effects of GCs, and suggest that prior exposure to GC excess is not associated with a persisting adverse outcome in the functional phenotype of the fibroblasts. 152 895-902 European Journal of Endocrinology

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Section: Discussionsupporting

confidence: 92%

The impact of chronic in vivo glucocorticoid excess on the functional characteristics of human skin fibroblasts obtained from patients with endogenous Cushing’s syndrome

Zervolea

Pratsinis²,

Tsagarakis³

et al. 2005

eur j endocrinol

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“…In particular, conditioned media (CM) from these cell strains were collected, and the amount of total and active TGF-β secreted was estimated. In agreement with the extended lifespan of CF, these cells secrete lower lev- els of active TGF-β in their milieu (Pratsinis et al 2002), and -maybe, more importantly -the average active TGF-β as a percentage of the total is significantly lower in CF than in NF (Table 3). In addition, as reactive oxygen species (ROS) have been inversely related with cellular longevity and ageing in general (Finkel and Holbrook 2000), the internal ROS content in both CF and NF was estimated, after incubation of the cells with the fluorescent substrate DCFH-DA.…”

Section: Fibroblasts From Cushing's Syndrome Patients Exhibit An Incrsupporting

confidence: 56%

The Unexpected Anabolic Phenotype and Extended Longevity of Skin Fibroblasts after Chronic Glucocorticoid Excess

et al. 2006

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Intense stress can challenge tissue homeostasis and accelerate the ageing process. However, several lines of evidence indicate that repeated mild stresses can have beneficial and even life-prolonging effects. Hypersecretion of glucocorticoids (GC) represents the major hormonal response to stress. Besides its life-sustaining role, GC excess, usually due to several side-effects that promote a "catabolic" phenotype, can be detrimental for several tissues. Cushing's syndrome patients are characterized by chronic endogenous GC excess and consequently at the time of diagnosis they have an atrophic elderly-like skin. Interestingly, when Cushing's syndrome fibroblasts were removed from the high-GC milieu in vivo and cultured in vitro under standard conditions they express an "anabolic" phenotype, i.e. they restore their ability for collagen synthesis, they secrete reduced levels of metalloproteases (MMP-1 and MMP-2) and have an increased proliferative capacity and contractility. Furthermore, these cells exhibit a significant extension of their proliferative lifespan, while they respond better to exogenous stress by producing significantly higher levels of heat-shock protein-70 (HSP70). These results imply that long-term hypercortisolism in vivo can have beneficial consequences on fibroblast physiology in vitro.

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“…Protein quality is crucial for cellular homeostasis and the presence of mis folding proteins is a common feature of the cells under oxidative stress Chaperon proteins, including HSP70 and 90, play roles in the degradation and refolding of proteins preventing from protein aggregation and cellular death. Several studies have reported age-associated decline in protein quality and responsiveness of HSP70 and HSP90 in tissues [38][39][40]. In addition, as the follicle grows, the expression level of HSP 60, HSP70, and HSP90 increases in bovine granulosa cells [41].…”

Section: Discussionmentioning

confidence: 99%

Age-associated changes in bovine oocytes and granulosa cell complexes collected from early antral follicles

Itami

Kawahara-Miki

Kawana

et al. 2014

J Assist Reprod Genet

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Chronic in vivo exposure to glucocorticoids prolongs cellular lifespan: the case of Cushing's syndrome-patients' fibroblasts

Cited by 20 publications

References 44 publications

The impact of chronic in vivo glucocorticoid excess on the functional characteristics of human skin fibroblasts obtained from patients with endogenous Cushing’s syndrome

The impact of chronic in vivo glucocorticoid excess on the functional characteristics of human skin fibroblasts obtained from patients with endogenous Cushing’s syndrome

The Unexpected Anabolic Phenotype and Extended Longevity of Skin Fibroblasts after Chronic Glucocorticoid Excess

Age-associated changes in bovine oocytes and granulosa cell complexes collected from early antral follicles

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