Shear stress regulates expression of death‐associated protein kinase in suppressing TNFα‐induced endothelial apoptosis

Rennier, Keith; Ji, Julie Y.

doi:10.1002/jcp.22975

Cited by 20 publications

(26 citation statements)

References 36 publications

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“…Previous studies have shown that shear stress can affect apoptosis in different cell types such as endothelial cells [66–68], osteoblasts [8], and tumor cells [9]. In the cornea, Yamamoto et al .…”

Section: Resultsmentioning

confidence: 99%

Corneal epithelial cells exposed to shear stress show altered cytoskeleton and migratory behaviour

et al. 2017

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Cells that form the corneal epithelium, the outermost layer of the cornea, are exposed to shear stress through blinking during waking hours. In this in vitro study, the effect of fluid shear stress on human corneal epithelial cells (HCECs) was investigated. Following exposure to shear stresses of 4 and 8 dyn/cm2, HCECs showed cytoskeletal rearrangement with more prominent, organized and elongated filamentous actin. Cytoskeletal changes were time-dependent, and were most significant after 24 hours of shear stress. Higher rates of migration and proliferation, as evaluated by a scratch assay, were also observed following 24 hours of low shear stress exposure (4 dyn/cm2). This result contrasted the poor migration observed in samples scratched before shear exposure, indicating that shear-induced cytoskeletal changes played a key role in improved wound healing and must therefore precede any damage to the cell layer. HCEC cytoskeletal changes were accompanied by an upregulation in integrin β1 and downregulation of ICAM-1. These results demonstrate that HCECs respond favourably to flow-induced shear stress, impacting their proliferation and migration properties as well as phenotype.

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Section: Resultsmentioning

confidence: 99%

Corneal epithelial cells exposed to shear stress show altered cytoskeleton and migratory behaviour

et al. 2017

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“…A previous study identified that DAPK functioned as a positive mediator of apoptosis induced by various stimuli, including TNF-α, interferon-γ and p53 (29). It was previously reported that DAPK activity may be involved in TNF-α-induced apoptotic pathways in bovine aortic endothelial cells (20). To the best of our knowledge, the present study is the first to reported that Hcy treatment increased mRNA and protein DAPK expression levels.…”

Section: Discussionmentioning

confidence: 99%

“…DAPK is upstream of the caspases, with the exception of caspase 8, and may induce caspase-independent cell death or autophagy. Previous studies have determined that DAPK contributed to shear stress-induced endothelial apoptosis (20,21). However, the importance of DAPK in Hcy-induced apoptosis in endothelial cells remains to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Upregulation of DAPK contributes to homocysteine-induced endothelial apoptosis via the modulation of Bcl2/Bax and activation of caspase 3

Tian

Shi

Liu

et al. 2016

Molecular Medicine Reports

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Hyperhomocysteinemia is characterized by an abnormally high level of homocysteine (Hcy) in the blood and is associated with cardiovascular diseases such as atherosclerosis. Endothelial dysfunction may lead to the pro-atherogenic effects associated with hyperhomocysteinemia. Endothelial dysfunction induced by Hcy has been previously investigated; however, the underlying molecular mechanism remains to be fully elucidated. The present study investigated whether death-associated protein kinase (DAPK) is involved in Hcy-induced apoptosis in human umbilical vein endothelial cells (HUVECs). It was determined that Hcy treatment upregulated the mRNA and protein expression levels of DAPK in HUVECs. Additionally, it was identified that the knockdown of DAPK using small interfering RNA may attenuate the Hcy-induced apoptosis and dissipation of mitochondrial membrane potential. DAPK inhibition may also reverse the effect of Hcy by the upregulation of B cell leukemia/lymphoma 2 (Bcl2) and poly ADP-ribose polymerase, and the downregulation of Bcl2-associated X protein (Bax) and of caspase 3. In conclusion, the present study demonstrated that DAPK contributed to the Hcy-induced endothelial apoptosis via modulation of Bcl2/Bax expression levels and activation of caspase 3.

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“…1,2 Tumor necrosis factor (TNF) α activates PKCζ in EC 1 and induces its apoptosis, 3,4 which contributes to vascular diseases such as atherosclerosis. 5 We are, therefore, interested in the mechanism of PKCζ-dependent EC apoptosis in response to TNFα stimulation.…”

mentioning

confidence: 99%

p62 Binding to Protein Kinase C ζ Regulates Tumor Necrosis Factor α–Induced Apoptotic Pathway in Endothelial Cells

Kim

Nigro

Fujiwara

et al. 2012

ATVB

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Objective Protein kinase C (PKC) ζ is a key pathological mediator of endothelial cell apoptosis. p62 is a scaffold protein that regulates several cell signaling pathways by binding to target proteins. Because PKCζ and p62 contain Phox/Bem1p (PB1) modules that mediate protein–protein interactions, we hypothesized that an interaction between p62 and PKCζ is required for tumor necrosis factor α–induced PKCζ signaling in endothelial cells. Methods and Results In human umbilical vein endothelial cell, tumor necrosis factor α (10 ng/mL) enhanced the interaction between p62 and PKCζ. Transfection with p62 small interfering RNA reduced the activation of both PKCζ and its downstream targets JNK and caspase 3, suggesting that p62 is necessary for PKCζ signaling. Overexpression of only the PB1 domain of p62 inhibited p62–PKCζ interaction, showing that binding of these 2 proteins is mediated by their PB1 domains. Furthermore, overexpression of the p62 PB1 domain suppressed tumor necrosis factor α–induced PKCζ activation and subsequent activation of JNK and caspase 3. Finally, transfection of either p62 small interfering RNA or the PB1 domain of p62 inhibited human umbilical vein endothelial cell apoptosis. Conclusion Our results suggest a novel function of p62 that regulates the activity of PKCζ by binding to PKCζ, thereby activating the PKCζ-JNK-caspase 3 apoptotic pathway in endothelial cells.

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Shear stress regulates expression of death‐associated protein kinase in suppressing TNFα‐induced endothelial apoptosis

Cited by 20 publications

References 36 publications

Corneal epithelial cells exposed to shear stress show altered cytoskeleton and migratory behaviour

Corneal epithelial cells exposed to shear stress show altered cytoskeleton and migratory behaviour

Upregulation of DAPK contributes to homocysteine-induced endothelial apoptosis via the modulation of Bcl2/Bax and activation of caspase 3

p62 Binding to Protein Kinase C ζ Regulates Tumor Necrosis Factor α–Induced Apoptotic Pathway in Endothelial Cells

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