Deep Hypothermia Markedly Activates the Small Ubiquitin-Like Modifier Conjugation Pathway; Implications for the Fate of Cells Exposed to Transient Deep Hypothermic Cardiopulmonary Bypass

Yang, Wei; Ma, Qing; Mackensen, G. Burkhard; Paschen, Wulf

doi:10.1038/jcbfm.2009.16

Cited by 34 publications

(48 citation statements)

References 17 publications

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“…SUMO induction following cooling of mammalian cells has been reported previously (Lee et al 2007(Lee et al , 2014Yang et al 2009;Wang et al 2012), and herein we demonstrate that the RNA exosome is a target for SUMO conjugation in cooled cells. Expression of EXOSC10 is reduced upon cooling both in cell lines and in vivo, which we correlate with perturbation of multiple 3 ′ ribosomal RNA (rRNA) processing activities associated with EXOSC10.…”

Section: Introductionsupporting

confidence: 83%

“…Interestingly, global SUMOylation has also been observed to increase in multiple cell and animal models of cooling (Lee et al 2007(Lee et al , 2014Yang et al 2009;Wang et al 2012). To investigate this as a possible mechanism by which ribosome synthesis is perturbed by cold, we analyzed global SUMOylation in cooled HEK293 cells.…”

Section: Global Sumoylation Is Increased By Mild Hypothermiamentioning

confidence: 99%

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Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

Knight

Bastide

Peretti

et al. 2016

RNA

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The RNA exosome is essential for 3 ′ processing of functional RNA species and degradation of aberrant RNAs in eukaryotic cells. Recent reports have defined the substrates of the exosome catalytic domains and solved the multimeric structure of the exosome complex. However, regulation of exosome activity remains poorly characterized, especially in response to physiological stress. Following the observation that cooling of mammalian cells results in a reduction in 40S:60S ribosomal subunit ratio, we uncover regulation of the nuclear exosome as a result of reduced temperature. Using human cells and an in vivo model system allowing whole-body cooling, we observe reduced EXOSC10 (hRrp6, Pm/Scl-100) expression in the cold. In parallel, both models of cooling increase global SUMOylation, leading to the identification of specific conjugation of SUMO1 to EXOSC10, a process that is increased by cooling. Furthermore, we define the major SUMOylation sites in EXOSC10 by mutagenesis and show that overexpression of SUMO1 alone is sufficient to suppress EXOSC10 abundance. Reducing EXOSC10 expression by RNAi in human cells correlates with the 3 ′ preribosomal RNA processing defects seen in the cold as well as reducing the 40S:60S ratio, a previously uncharacterized consequence of EXOSC10 suppression. Together, this work illustrates that EXOSC10 can be modified by SUMOylation and identifies a physiological stress where this regulation is prevalent both in vitro and in vivo.

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Section: Introductionsupporting

confidence: 83%

Section: Global Sumoylation Is Increased By Mild Hypothermiamentioning

confidence: 99%

Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

Knight

Bastide

Peretti

et al. 2016

RNA

View full text Add to dashboard Cite

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“…That nuclear translocation of proteins may confer neuroprotection has been recently shown with other candidate therapeutic molecules in stroke (Gan et al, 2010; Pallast et al, 2010; Yang et al, 2008, 2009). The present data, therefore, strongly support the hypothesis that DJ-1 exerts significant control on both mitochondrial function and dynamic cell structure requiring a balance between fission and fusion.…”

Section: Discussionmentioning

confidence: 83%

DJ-1 ameliorates ischemic cell death in vitro possibly via mitochondrial pathway

Kaneko

Shojo

Burns

et al. 2014

Neurobiology of Disease

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DJ-1 is an important redox-reactive neuroprotective protein implicated in regulation of oxidative stress after ischemia. However the molecular mechanism, especially the mitochondrial function, by which DJ-1 protects neuronal cells in stroke remains to be elucidated. The aim of this study was to reveal whether DJ-1 translocates into the mitochondria in exerting neuroprotection against an in vitro model of stroke. Human neural progenitor cells (hNPCs) were initially exposed to oxygen–glucose deprivation and reperfusion injury, and thereafter, DJ-1 translocation was measured by immunocytochemistry and its secretion by hNPCs was detected by enzyme-linked immunosorbant assay (ELISA). Exposure of hNPCs to experimental stroke injury resulted in DJ-1 translocation into the mitochondria. Moreover, significant levels of DJ-1 protein were secreted by the injured hNPCs. Our findings revealed that DJ-1 principally participates in the early phase of stroke involving the mitochondrial pathway. DJ-1 was detected immediately after stroke and efficiently translocated into the mitochondria offering a new venue for developing treatment strategies against ischemic stroke.

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“…We demonstrated, for the first time, that when animals are exposed to various degrees of hypothermia ranging from 18°C to 30°C, both deep and moderate hypothermia activate the SUMOylation pathway, and induce nuclear accumulation of SUMO2/3-conjugated proteins. 22 23 Therefore, we proposed that SUMOylation contributes to the neuroprotection afforded by therapeutic hypothermia. This notion has been substantiated by the finding that hypothermic treatment has no additional protective effect on stroke outcome in Ubc9 transgenic mice, which sustain high levels of global SUMOylation.…”

Section: Cancermentioning

confidence: 99%

Targeting the SUMO pathway for neuroprotection in brain ischaemia

2016

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Small ubiquitin-like modifier (SUMO) conjugation (SUMOylation) is a post-translational protein modification that modulates almost all major cellular processes, and has been implicated in many human diseases. A growing body of evidence from in vitro and in vivo studies demonstrates that increasing global levels of SUMO conjugated proteins (global SUMOylation) protects cells against ischaemia-induced damage, while suppressing global SUMOylation promotes cell injury after ischaemia. Indeed, SUMOylation has emerged as a potential therapeutic target for neuroprotection in brain ischaemia, including global brain ischaemia and focal brain ischaemia (ischaemic stroke). Here, we summarise findings on the role of SUMOylation in human diseases, brain ischaemia in particular, and review recent developments in drug discovery targeting SUMOylation with a major focus on its neuroprotective applications.

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Deep Hypothermia Markedly Activates the Small Ubiquitin-Like Modifier Conjugation Pathway; Implications for the Fate of Cells Exposed to Transient Deep Hypothermic Cardiopulmonary Bypass

Cited by 34 publications

References 17 publications

Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis

DJ-1 ameliorates ischemic cell death in vitro possibly via mitochondrial pathway

Targeting the SUMO pathway for neuroprotection in brain ischaemia

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