Organ-specific alteration in caspase expression and STK3 proteolysis during the aging process

Lessard‐Beaudoin, Mélissa; Laroche, Mélissa; Loudghi, Amal; Demers, Marie-Josée; Denault, Jean‐Bernard; Grenier, Guillaume; Riechers, Sean-Patrick; Wanker, Erich E.; Graham, Rona K.

doi:10.1016/j.neurobiolaging.2016.07.003

Cited by 6 publications

(3 citation statements)

References 54 publications

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“…However, shmiR‐27a greatly increases the apoptosis of HaCaT cells and caspase‐3 activity. Caspase‐3 is reported to regulate various physiological functions such as cell apoptosis . Changes of caspase‐3 activity and the percentage of apoptosis cells after overexpression or knockdown of miR‐27a indicate suppression of UVB radiation‐induced cell apoptosis by miR‐27a.…”

Section: Discussionmentioning

confidence: 99%

MiRNA‐27a decreases ultraviolet B irradiation‐induced cell damage

Zhang

Yang

et al. 2019

J of Cellular Biochemistry

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MiRNAs were involved in the various biological process through mediating the posttranscriptional gene silencing. The abnormal expression of miRNAs is also involved in various disorders. Our previous study showed that miRNA‐27a (miR‐27a) was upregulated after ultraviolet B (UVB) irradiation. However, the function of miR‐27a in UVB‐induced cell damage is still unclear. In this study, we used the miR‐27a overexpression and knockdown lentivirus to transfect UVB irradiated HaCaT cell line and observed the influence of miR‐27a on UVB irradiated damages in cells. We found that miR‐27a removed cyclobutane pyrimidine dimers (CPDs) and decreased the cell apoptosis after UVB radiation. Further studies showed that miR‐27a directly decreased the expression and luciferase activity of target genes transactive response DNA‐binding protein (TARDBP) and apoptotic protease activating factor‐1 (APAF‐1). In conclusion, miR‐27a can inhibit CPDs, reduce the cell apoptosis and down‐regulate its target genes TARDBP and APAF‐1 induced by UVB irradiation in HaCaT cells. It is indicated that miR‐27a may serve as a target for UVB irradiation protection.

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Section: Discussionmentioning

confidence: 99%

MiRNA‐27a decreases ultraviolet B irradiation‐induced cell damage

Zhang

Yang

et al. 2019

J of Cellular Biochemistry

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“…To the best of our knowledge, casp9 has never been shown to cleave STK3 or DAXX, nor are any of the described casp9 recognition sites present in these proteins. STK3 can be cleaved by casp3 (Deng et al, ; Lee et al, ; Lessard Beaudoin et al, ), but it should be noted that casp3 is not essential for the endogenous cleavage of STK3 (as has been shown for casp6) (Riechers et al, ). Future experiments using caspase inhibitors may help to resolve this issue.…”

Section: Discussionmentioning

confidence: 99%

Activation of caspase‐6 and cleavage of caspase‐6 substrates is an early event in NMDA receptor–mediated excitotoxicity

Girling

Demers

Lainé

et al. 2017

J of Neuroscience Research

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Excitotoxicity, due to overstimulation of N-methyl D-aspartate receptors (NMDARs), has a pivotal role in many neurological disorders. However, NMDAR antagonists often cause side effects, and identifying more druggable therapeutic targets for NMDAR excitotoxicity is an important goal. Activation of caspases is a downstream effect of excitotoxicity that may be critically involved in NMDAR-mediated cell death. Caspase-6 (casp6) in particular has been shown to play a key role in the pathogenesis of stroke, Huntington disease, and Alzheimer disease. Using N-methyl D-aspartate (NMDA)-induced excitotoxic injuries of primary rat neurons, we demonstrate that there is an early increase in caspase profiles after an excitotoxic event at the level of mRNA, protein, and activity. Casp6 is elevated and activated first, followed by caspase-8 and caspase-3. Similarly, known casp6 substrates huntingtin, as well as novel casp6 substrates serine/threonine kinase 3 and death domain-associated protein, are cleaved in similar temporal patterns post NMDA. On the basis of these data, we propose that casp6 may be an initiator caspase in apoptotic cascades leading to neuronal death after an excitotoxic event and suggest casp6 as a potential therapeutic target for neurological disorders where NMDAR-mediated excitotoxicity has been shown to play a role.

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“…MST2 regulates the proliferation, differentiation, and apoptosis of tumor growth and the immune system [17][18][19][20]. MST2 has important roles in the neuronal system, such as neuronal apoptotic death [21], the aging process [22], huntingtin disease [23], and retinal detachment (RD) [24]. MST2 regulates microtubule stability/dynamics in a noncanonical way.…”

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confidence: 99%

MST2 Acts via AKT Activity to Promote Neuronal Axon Regeneration and Functional Recovery after Spinal Cord Injury in Mice

Zheng

Wang

et al. 2023

Preprint

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Background Mammalian sterile 20-like kinase 2 (MST2), a core component of the Hippo signaling pathway, plays an crucial role in apoptosis and cell growth. However, its role in axon regeneration after spinal cord injury (SCI) was first elucidated in this study. Methods We first screened the proteins involved in spinal cord contusion injury using a mouse model utilizing 4D label-free proteomic analysis. We selected the neuronal axon regeneration-associated protein MST2 as our target protein. In vitro and in vivo experiments were applied to explore the function of MST2. We then performed additional experiments, such as co-immunoprecipitation and so on to confrm the downstream molecular mechanisms of MST2. Results We confirmed that MST2, mainly expressed in neurons, promoted axon regeneration by positively regulating AKT activity in neuronal cell models and primary cortical neurons. Mechanistically, our studies found that MST2 protein could interact both with AKT and p-AKT in vitro. In vivo, MST2 knockdown inhibits axon regeneration and motor functional recovery, while lentiviral-mediated overexpression of MST2 promoted axon regeneration and motor functional recovery after SCI. However, MST2 induced axon regeneration and motor functional recovery were reversed by AKT inhibitors. Conclusion This study provided evidence that how MST2 acts as a new regulator that controls axon regeneration after SCI, MST2 promotes neuronal axon regeneration by positively regulating AKT activity, indicating MST2 may be a target with great therapeutic potential for SCI.

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Organ-specific alteration in caspase expression and STK3 proteolysis during the aging process

Cited by 6 publications

References 54 publications

MiRNA‐27a decreases ultraviolet B irradiation‐induced cell damage

MiRNA‐27a decreases ultraviolet B irradiation‐induced cell damage

Activation of caspase‐6 and cleavage of caspase‐6 substrates is an early event in NMDA receptor–mediated excitotoxicity

MST2 Acts via AKT Activity to Promote Neuronal Axon Regeneration and Functional Recovery after Spinal Cord Injury in Mice

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