Sirt1 modulates premature senescence-like phenotype in human endothelial cells

Ota, Hidetaka; Akishita, Masahiro; Eto, Masato; Iijima, Katsuya; Kaneki, Masao; Ouchi, Yasuyoshi

doi:10.1016/j.yjmcc.2007.08.008

Cited by 383 publications

(312 citation statements)

References 43 publications

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“…One of POZ/BTB protein member, HIC1 was reported to bind to SIRT1 through its POZ domain. 29 As SIRT1 is known to modulate premature senescence-like phenotype in human ECs, 35 we measured binding of PATZ1 protein to SIRT1 by immunoprecipitation. We confirmed that the SIRT1 protein level decreased in old cells and PATZ1 was bound to SIRT1 (Supplementary Figure 6).…”

Section: Discussionmentioning

confidence: 99%

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway

Cho

Kim

et al. 2011

Cell Death Differ

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Vascular cell senescence, induced by the DNA damage response or inflammatory stress, contributes to age-associated vascular disease. Using complementary DNA microarray technology, we found that the level of POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) is downregulated during endothelial cell (EC) senescence. PATZ1 may have an important role as a transcriptional repressor in chromatin remodeling and transcription regulation; however, the role of PATZ1 in EC senescence and vascular aging remains unidentified. Knockdown of PATZ1 in young cells accelerated premature EC senescence, which was confirmed by growth arrest, increased p53 protein level and senescence-associated b-galactosidase (SA-b-gal) activity, and repression of EC tube formation. In contrast, overexpression of PATZ1 in senescent cells reversed senescent phenotypes. Cellular senescence induced by PATZ1 knockdown in young cells was rescued by knockdown of p53, but not by knockdown of p16 INK4a . PATZ1 knockdown increased ROS levels, and pretreatment with N-acetylcysteine abolished EC senescence induced by PATZ1 knockdown. Notably, PATZ1 immunoreactivity was lower in ECs of atherosclerotic tissues than those of normal arteries in LDLR À/À mice, and immunoreactivity also decreased in ECs of old human arteries. These results suggest that PATZ1 may have an important role in the regulation of EC senescence through an ROS-mediated p53-dependent pathway and contribute to vascular diseases associated with aging.

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Section: Discussionmentioning

confidence: 99%

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway

Cho

Kim

et al. 2011

Cell Death Differ

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“…As NO itself appears to reciprocally activate Sirt1 expression and activity (Ota et al 2007), then Sirt1-eNOS axis emerges as a decisive regulatory mechanism in CC endothelium.…”

Section: Discussionmentioning

confidence: 99%

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Tomada

Almeida

et al. 2011

AGE

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Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD + -dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.

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“…3, both compounds induced p53 acetylation, which is critical for expression of miR-34a, leading to radiosensitization effects. Because Sirt1 is one of the well known deacetylases for p53, we hypothesized that Sirt1 might be a potential target of rhamnetin and cirsiliol (82). Rhamnetin and cirsiliol have very similar structures of fisetin and quercetin, which are known of Sirt1 activators (83).…”

Section: Difluorophenacetyl)-l-alanyl]-s-phenylgly-mentioning

confidence: 99%

Rhamnetin and Cirsiliol Induce Radiosensitization and Inhibition of Epithelial-Mesenchymal Transition (EMT) by miR-34a-mediated Suppression of Notch-1 Expression in Non-small Cell Lung Cancer Cell Lines

Kang

Kim

et al. 2013

Journal of Biological Chemistry

165

155

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Background: Notch-1 plays a critical role in cell fate decisions by modulating cellular processes under irradiation. Results: Irradiation-induced Notch-1 overexpression promoted survival and EMT in NSCLC, whereas rhamnetin and cirsiliol inhibited these effects via miR-34a-mediated Notch-1 down-regulation. Conclusion: Rhamnetin and cirsiliol suppress Notch-1-mediated radioresistance and EMT phenotypes in NSCLC. Significance: Rhamnetin and cirsiliol can act as novel radiosensitizers by inhibiting radiation-induced Notch-1 signaling.

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Sirt1 modulates premature senescence-like phenotype in human endothelial cells

Cited by 383 publications

References 43 publications

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway

POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1) inhibits endothelial cell senescence through a p53 dependent pathway

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Rhamnetin and Cirsiliol Induce Radiosensitization and Inhibition of Epithelial-Mesenchymal Transition (EMT) by miR-34a-mediated Suppression of Notch-1 Expression in Non-small Cell Lung Cancer Cell Lines

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