JAK Inhibitors and Oxidative Stress Control

Charras, Amandine; Arvaniti, Pinelopi; Dantec, Christelle Le; Dalekos, George Ν.; Zachou, K.; Bordron, Anne; Renaudineau, Yves

doi:10.3389/fimmu.2019.02814

Cited by 43 publications

(29 citation statements)

References 59 publications

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“…35 JAK/STAT signaling pathway participates in a variety of pathological processes and regulating JAK/STAT can alleviate cell damage caused by oxidative stress. 36 Activation of JAK1/STAT1 signaling was required for increased expression of Beclin-1 , a key regulator of autophagy, 37 which is consistent with our results showing that MPH treatment significantly increased the protein expression of p-JAK1/p-STAT1 in 661 W cells.…”

Section: Discussionsupporting

confidence: 88%

Methylphenidate causes cytotoxicity on photoreceptor cells via autophagy

et al. 2020

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Methylphenidate (MPH) is used as the first-line treatment for attention-deficit hyperactivity disorder. However, there are concerns that this treatment may be associated with increased risk of retinal damage. This study was to investigate cytotoxicity of MPH on photoreceptor cells and explore its underlying mechanisms. MPH-caused cell toxicity was established in 661 W cells. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium-bromid and lactate dehydrogenase assays. Oxidative stress was measured by the markers: glutathione (GSH) reductase, catalase, and superoxide dismutase activities as well as GSH, reactive oxygen species, and malondialdehyde levels. Gene and protein expression was detected by real-time polymerase chain reaction (PCR) and western blot, respectively. Results showed that MPH decreased 661 W cell viability, increased caspase-3/9 activities, and induced oxidative stress. Furthermore, MPH treatment increased messenger RNA (mRNA) expression of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3B (LC3B) protein expression in 661 W cells, suggesting autophagy was induced. MPH treatment also upregulated p-JAK1/p-STAT1 protein expression. These data demonstrated that MPH could increase oxidative stress in photoreceptor cells to cause cell toxicity via autophagy, providing the scientific rationale for the photoreceptor cell damage caused by the MPH administration.

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Section: Discussionsupporting

confidence: 88%

Methylphenidate causes cytotoxicity on photoreceptor cells via autophagy

et al. 2020

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“…The blockade of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling may be considered of therapeutic applicability in pSS. It is well known that the use of JAK inhibitors in pSS is promising because suppression of the JAK/STAT pathway improves sicca manifestations [ 113 , 114 ]. Pringle et al demonstrated, recently, that SG precursor cells react to pro-inflammatory cytokines by proliferation and apparent cell death, presumably by signalling through the JAK/STAT pathway, implying that inhibitors of JAK/STAT signalling may also interfere with the homeostasis of the SG epithelium [ 115 ].…”

Section: Future Perspectives On Alternative Molecular Mechanisms Mmentioning

confidence: 99%

SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

Sisto

Ribatti

Lisi

2021

IJMS

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There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjögren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS salivary glands (SGs) as mediator of the epithelial-mesenchymal transition (EMT) activation. Although EMT seems to cause pSS SG fibrosis, TGF-β family members have ambiguous effects on the function of pSS SGs. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

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“…The blockade of Janus chinasi (JAK)/signal transducer and activator of transcription (STAT) signalling may be considered of therapeutic applicability in pSS. It is well known that the use of JAK inhibitors in pSS is promising because suppression of the JAK/STAT pathway improves sicca manifestations [114,115]. Pringle et al demonstrated, recently, that SG precursor cells react to pro-inflammatory cytokines by proliferation and apparent cell death, presumably by signalling through the JAK/STAT pathway, implying that inhibitors of JAK/STAT signalling may also interfere with the homeostasis of the SG epithelium [116].…”

Section: Smad7 Functions As Inhibitor Of Jak/stat Pathway In Ssmentioning

confidence: 99%

SMADS-mediate Molecular Mechanisms in Sjӧgren's Syndrome

Sisto¹,

Ribatti²,

Lisi³

2021

Preprint

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There is considerable interest in delineating the molecular mechanisms of action of transforming growth factor-β (TGF-β), considered as central player in a plethora of human conditions, including cancer, fibrosis and autoimmune disease. TGF-β elicits its biological effects through membrane bound serine/threonine kinase receptors which transmit their signals via downstream signalling molecules, SMADs, which regulate the transcription of target genes in collaboration with various co-activators and co-repressors. Until now, therapeutic strategy for primary Sjӧgren’s syndrome (pSS) has been focused on inflammation, but, recently, the involvement of TGF-β/SMADs signalling has been demonstrated in pSS, although TGFβ family members seems to have ambiguous effects on the function of pSS salivary glands. Based on these premises, this review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in pSS that are dictated by orchestrations of SMADs, and describe TGF-β/SMADs value as both disease markers and/or therapeutic target for pSS.

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JAK Inhibitors and Oxidative Stress Control

Cited by 43 publications

References 59 publications

Methylphenidate causes cytotoxicity on photoreceptor cells via autophagy

Methylphenidate causes cytotoxicity on photoreceptor cells via autophagy

SMADS-Mediate Molecular Mechanisms in Sjögren’s Syndrome

SMADS-mediate Molecular Mechanisms in Sjӧgren's Syndrome

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