p66shc is highly expressed in fibroblasts from centenarians

Pandolfi, Silvia; Bonafè, Massimiliano; Tella, L Di; Tiberi, Luca; Salvioli, Stefano; Monti, Daniela; Sorbi, Sandro; Franceschi, Claudio

doi:10.1016/j.mad.2005.03.004

Cited by 51 publications

(33 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such a selective response deserves further clarification. 26 Similar Shc genomic organization and Shc transcript assembly exist in mice and in humans. Alignment of the predicted translation of the mouse p66 shc sequence, as derived from analysis of p66 cDNAs with human p66…”

Section: Accordingly P66mentioning

confidence: 98%

See 1 more Smart Citation

Final Common Molecular Pathways of Aging and Cardiovascular Disease

Cosentino

Francia²,

Camici

et al. 2008

ATVB

158

124

View full text Add to dashboard Cite

Abstract-Oxidative stress affects the availability of key-regulators of vascular homeostasis and controls a number of signaling pathways relevant to myocardial and vascular disease. Reactive oxygen species are generated by different intracellular molecular pathways principally located in mitochondria. The notion that mice carrying a targeted mutation of the p66 Shc gene display prolonged lifespan, reduced production of intracellular oxidants, and increased resistance to oxidative stress-induced apoptosis prompted a series of studies aimed at defining the biochemical function of p66Shc and its possible implication in cardiovascular diseases. Indeed, p66ShcϪ/Ϫ mice are protected against vascular, cardiac, and renal impairment attributable to hypercholesterolemia, aging, diabetes, and ischemia/reperfusion. The present review focuses on the biochemical and physiological function of the p66Shc adaptor protein as well as on the mechanisms linking p66Shc -associated generation of free radicals to the pathophysiology of aging and cardiovascular disease. On the whole, the evidence so far reported and here discussed supports the concept that pharmacological modulation of p66

show abstract

Section: Accordingly P66mentioning

confidence: 98%

“…26 Treatment of dermal fibroblasts with the prooxidant 2-deoxy-D-ribose (dRib) strongly induced p66 Shc expression in all age groups. Conversely, hypoxia caused p66…”

Section: Accordingly P66mentioning

confidence: 99%

Final Common Molecular Pathways of Aging and Cardiovascular Disease

Cosentino

Francia²,

Camici

et al. 2008

ATVB

158

124

View full text Add to dashboard Cite

show abstract

“…Alternatively, p66Shc may regulate ROS production through SOS1-mediated Rac1 activation in these cells (Khanday et al, 2006). Interestingly, p66Shc has been proposed as one of the lifespan determinants by virtue of its apoptotic signaling in mouse models (Migliaccio et al, 1999), although its association with human longevity remains to be established (Pandolfi et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial redox signaling by p66Shc is involved in regulating androgenic growth stimulation of human prostate cancer cells

et al. 2008

View full text Add to dashboard Cite

p66Shc is shown to negatively regulate the life span in mice through reactive oxygen species (ROS) production. Recent reports, however, revealed that p66Shc protein level is significantly elevated in several human cancer tissues and growth-stimulated carcinoma cells, suggesting a mitogenic and carcinogenic role for p66Shc. In this communication, we demonstrate for the first time that p66Shc mediates androgenic growth signals in androgen-sensitive human prostate cancer cells through mitochondrial ROS production. Growth stimulation of prostate cancer cells with 5a-dihydrotestosterone (DHT) is accompanied by increased p66Shc level and ROS production, which is abolished by antioxidant treatments. However, antioxidant treatments do not affect the transcriptional activity of androgen receptor (AR) as observed by its inability to block DHTinduced prostate-specific antigen expression, an AR-dependent correlate of prostate cancer progression. Elevated expression of p66Shc by cDNA transfection increases the basal cell proliferation and, thus, reduces additional DHTinduced cell proliferation. Furthermore, DHT increases the translocation of p66Shc into mitochondria and its interaction with cytochrome c. Conversely, both redox-negative p66Shc mutant (W134F), which is deficient in cytochrome c interaction, and p66Shc small interfering RNA decrease DHT-induced cell proliferation. These results collectively reveal a novel role for p66Shc-ROS pathway in androgeninduced prostate cancer cell proliferation and, thus, may play a role in early prostate carcinogenesis.

show abstract

“…In particular, in some cases studies on animal models have led to analogous results also in humans, as in the case of Insulin/IGF-1 signaling pathway , while in other cases results obtained in animal models have not been reproducible in humans. For example, the knock out of p66 Shc gene leads to an increase in mice lifespan (Migliaccio et al, 1999) and consequently it has been hypothesised that centenarians should hypoexpress this gene (Purdom and Chen, 2003), while, on the contrary we observed that dermal fibroblasts from centenarians do have higher levels of p66 Shc mRNA and protein with respect to young and middle-aged subjects (Pandolfi et al, 2005). Thus, often it appears not sufficiently adequate the animal model for the study of human longevity Capri et al, 2006).…”

Section: Discussionmentioning

confidence: 64%