Integrating role of T antigen, Rb2/p130, CTCF and BORIS in mediating non-canonical endoplasmic reticulum-dependent death pathways triggered by chronic ER stress in mouse medulloblastoma

Macaluso, Marcella; Caracciolo, Valentina; Rizzo, Valeria; Sun, Ang; Montanari, Micaela; Russo, Giuseppe; Bellipanni, Gianfranco; Khalili, Kamel; Giordano, Antonio

doi:10.4161/cc.20242

Cited by 13 publications

(9 citation statements)

References 17 publications

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“…LPS-treated N4-2C-RA cells (1 £ 10 6 /ml) and untreated N4-2C-RA cells (1 £ 10 6 /ml) were washed with PBS, fixed in 70% (v/v) ethanol and stored at 4 C, according to protocols wellestablished in the laboratory. 42 The cells were then centrifuged at 1,000 rpm, washed twice with PBS, and the pellets were resuspended in 0.4 ml of freshly prepared PBS solution containing 50 mg/ml of propidium iodide (PI) and 0.2 mg/ml of RNase (Abcam, Cambridge, UK)29. The stained samples were incubated 30 min at 37 C and analyzed by using an Accuri C6 Flow Cytometer (Accuri, Bioscience San Jose, CA).…”

Section: Cell Cycle Analysismentioning

confidence: 99%

LPS-induced inflammatory response triggers cell cycle reactivation in murine neuronal cells through retinoblastoma proteins induction

et al. 2017

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Cell cycle reactivation in adult neurons is an early hallmark of neurodegeneration. The lipopolysaccharide (LPS) is a well-known pro-inflammatory factor that provokes neuronal cell death via glial cells activation. The retinoblastoma (RB) family includes RB1/p105, retinoblastoma-like 1 (RBL1/p107), and retinoblastomalike 2 (Rb2/p130). Several studies have indicated that RB proteins exhibit tumor suppressor activities, and play a central role in cell cycle regulation. In this study, we assessed LPS-mediated inflammatory effect on cell cycle reactivation and apoptosis of neuronally differentiated cells. Also, we investigated whether the LPS-mediated inflammatory response can influence the function and expression of RB proteins. Our results showed that LPS challenges triggered cell cycle reactivation of differentiated neuronal cells, indicated by an accumulation of cells in S and G2/M phase. Furthermore, we found that LPS treatment also induced apoptotic death of neurons. Interestingly, we observed that LPS-mediated inflammatory effect on cell cycle re-entry and apoptosis was concomitant with the aberrant expression of RBL1/p107 and RB1/p105. To the best of our knowledge, our study is the first to indicate a role of LPS in inducing cell cycle re-entry and/or apoptosis of differentiated neuronal cells, perhaps through mechanisms altering the expression of specific members of RB family proteins. This study provides novel information on the biology of post-mitotic neurons and could help in identifying novel therapeutic targets to prevent de novo cell cycle reactivation and/or apoptosis of neurons undergoing neurodegenerative processes.

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Section: Cell Cycle Analysismentioning

confidence: 99%

LPS-induced inflammatory response triggers cell cycle reactivation in murine neuronal cells through retinoblastoma proteins induction

et al. 2017

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“…Recently, perinuclear localization of Ctcf has been observed to be dependent on ER stress in mouse medulloblastoma cell lines [47]. In this regard, the lack of nuclear PARylation could induce ER stress-dependent Ctcf cellular re-localization.…”

Section: Discussionmentioning

confidence: 99%

ADP-ribose polymer depletion leads to nuclear Ctcf re-localization and chromatin rearrangement

Guastafierro

Catizone

Calabrese

et al. 2013

Biochemical Journal

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Ctcf (CCCTC-binding factor) directly induces Parp [poly(ADP-ribose) polymerase] 1 activity and its PARylation [poly(ADPribosyl)ation] in the absence of DNA damage. Ctcf, in turn, is a substrate for this post-synthetic modification and as such it is covalently and non-covalently modified by PARs (ADP-ribose polymers). Moreover, PARylation is able to protect certain DNA regions bound by Ctcf from DNA methylation. We recently reported that de novo methylation of Ctcf target sequences due to overexpression of Parg [poly(ADP-ribose)glycohydrolase] induces loss of Ctcf binding. Considering this, we investigate to what extent PARP activity is able to affect nuclear distribution of Ctcf in the present study. Notably, Ctcf lost its diffuse nuclear localization following PAR (ADP-ribose polymer) depletion and accumulated at the periphery of the nucleus where it was linked with nuclear pore complex proteins remaining external to the perinuclear Lamin B1 ring. We demonstrated that PAR depletion-dependent perinuclear localization of Ctcf was due to its blockage from entering the nucleus. Besides Ctcf nuclear delocalization, the outcome of PAR depletion led to changes in chromatin architecture. Immunofluorescence analyses indicated DNA redistribution, a generalized genomic hypermethylation and an increase of inactive compared with active chromatin marks in Parg-overexpressing or Ctcf-silenced cells. Together these results underline the importance of the cross-talk between Parp1 and Ctcf in the maintenance of nuclear organization.

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“…Both treated and untreated ARPE‐19 cells (1 × 10 6 /ml) were washed with PBS, fixed in 70% (v/v) ethanol and stored at 4 °C, according to protocols well‐established in the lab (Macaluso et al, ).…”

Section: Methodsmentioning

confidence: 99%

Effect of sex steroid hormone fluctuations in the pathophysiology of male‐retinal pigment epithelial cells

Astarita¹,

D'Angelo-Maansson²,

Massaro-Giordano

et al. 2018

Journal Cellular Physiology

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Gender-based differences may influence the occurrence of several ocular conditions suggesting the possibility that fluctuations in sex steroid homeostasis may have direct effects on the eye physiology. Here, we evaluated the effect of sex steroid hormone fluctuations in male retinal pigment epithelial cells, RPEs (ARPE-19). To mimic hormonal fluctuations occurring during aging, we exposed ARPE-19 to acute, prolonged or chronic estradiol, and progesterone challenges. We found that chronic estradiol treatment promotes a remarkable necrosis of RPE cells, and does not affect pRb2/p130 or PAI-2 sub-cellular localization. In contrast, chronic progesterone exposure induces nuclear subcellular rearrangement of pRb2/p130, co-immunolocalization of pRb2/p130 with PAI-2, and accumulation of cells in G2/M phase, which is accompanied by a remarkable reduction of necrosis in favour of apoptosis activation. This study has a high clinical significance since it considers sex steroid fluctuations as inducers of milieu change in the retina able to influence pathological situations occurring with aging in non-reproductive systems such as the eye. Exogenous administration of physiologically significant amounts of sex hormones for long periods of time is a common clinical practice for transgender patients seeking sex reassignment. In particular, our study offers the unique opportunity to unravel the effects of sex hormones, not only in determining gender differences but also in affecting the physiology of non-reproductive systems, such as the eye, in the underserved transgender community.

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Integrating role of T antigen, Rb2/p130, CTCF and BORIS in mediating non-canonical endoplasmic reticulum-dependent death pathways triggered by chronic ER stress in mouse medulloblastoma

Abstract: (2012) Integrating role of T antigen, Rb2/p130, CTCF and BORIS in mediating non-canonical endoplasmic reticulum-dependent death pathways triggered by chronic ER stress in mouse medulloblastoma,

Cited by 13 publications

References 17 publications

LPS-induced inflammatory response triggers cell cycle reactivation in murine neuronal cells through retinoblastoma proteins induction

LPS-induced inflammatory response triggers cell cycle reactivation in murine neuronal cells through retinoblastoma proteins induction

ADP-ribose polymer depletion leads to nuclear Ctcf re-localization and chromatin rearrangement

Effect of sex steroid hormone fluctuations in the pathophysiology of male‐retinal pigment epithelial cells

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