Role of UCHL1 in Radiation-Induced Lung Injury Mediated by Sphingolipids

Epshtein, Yulia; Wang, H.; Jacobson, J.R.

doi:10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2108

Cited by 2 publications

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“…Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), also named as pGp 9.5, can function as a deubiquitinating enzyme in monomeric form and an ubiquitin ligase in dimer or oligomeric form [ 17 ]. Abnormal expression of UCH-L1 has been reported to be implicated in the pathogenesis of multiple diseases such as cancers [ 18 ], nervous system diseases [ 19 ] and lung injury [ 20 ]. Moreover, previous studies showed that UCH-L1 was selectively and abundantly expressed in multiple reproductive cells such as oocytes, spermatogonia and testis cells [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

UCH-L1 inhibitor LDN-57444 hampers mouse oocyte maturation by regulating oxidative stress and mitochondrial function and reducing ERK1/2 expression

et al. 2020

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Oocyte maturation is a prerequisite for successful fertilization and embryo development. Incomplete oocyte maturation can result in infertility. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) has been found to be implicated in oocyte maturation and embryo development. However, the cellular and molecular mechanisms of UCH-L1 underlying oocyte maturation have not been fully elucidated. In the present study, we observed that the introduction of UCH-L1 inhibitor LDN-57444 suppressed first polar body extrusion during mouse oocyte maturation. The inhibition of UCH-L1 by LDN-57444 led to the notable increase of reactive oxygen species (ROS) level, conspicuous reduction of glutathione (GSH) content and mitochondrial membrane potential (MMP), and blockade of spindle body formation. As a conclusion, UCH-L1 inhibitor LDN-57444 suppressed mouse oocyte maturation by improving oxidative stress, attenuating mitochondrial function, curbing spindle body formation and down-regulating ERK1/2 expression, providing a deep insight into the cellular and molecular basis of UCH-L1 during mouse oocyte maturation.

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Section: Introductionmentioning

confidence: 99%

UCH-L1 inhibitor LDN-57444 hampers mouse oocyte maturation by regulating oxidative stress and mitochondrial function and reducing ERK1/2 expression

et al. 2020

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“…Subsequently, we used a pharmacologic UCHL1 inhibitor, LDN-57444, and confirmed augmented RILI associated with UCHL1 inhibition. Finally, in separate experiments, EC SphK1 levels were inversely affected by UCHL1-silencing and overexpression while inhibition of SphK1 resulted in decreased basal and radiation-induced EC UCHL1 expression [38].…”

Section: Uchl1mentioning

confidence: 87%

Sphingolipids as a Novel Therapeutic Target in Radiation-Induced Lung Injury

Jacobson

2021

Cell Biochem Biophys

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Radiation-induced lung injury (RILI) is a potential complication of thoracic radiotherapy that can result in pneumonitis or pulmonary fibrosis and is associated with significant morbidity and mortality. The pathobiology of RILI is complex and includes the generation of free radicals and DNA damage that precipitate oxidative stress, endothelial cell (EC), and epithelial cell injury and inflammation. While the cellular events involved continue to be elucidated and characterized, targeted and effective therapies for RILI remain elusive. Sphingolipids are known to mediate EC function including many of the cell signaling events associated with the elaboration of RILI. Sphingosine-1-phosphate (S1P) and S1P analogs enhance EC barrier function in vitro and have demonstrated significant protective effects in vivo in a variety of acute lung injury models including RILI. Similarly, statin drugs that have pleiotropic effects that include upregulation of EC S1P receptor 1 (S1PR1) have been found to be strongly protective in a small animal RILI model. Thus, targeting of EC sphingosine signaling, either directly or indirectly, to augment EC function and thereby attenuate EC permeability and inflammatory responses, represents a novel and promising therapeutic strategy for the prevention or treatment of RILI.

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Role of UCHL1 in Radiation-Induced Lung Injury Mediated by Sphingolipids

Cited by 2 publications

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UCH-L1 inhibitor LDN-57444 hampers mouse oocyte maturation by regulating oxidative stress and mitochondrial function and reducing ERK1/2 expression

UCH-L1 inhibitor LDN-57444 hampers mouse oocyte maturation by regulating oxidative stress and mitochondrial function and reducing ERK1/2 expression

Sphingolipids as a Novel Therapeutic Target in Radiation-Induced Lung Injury

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