Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema

Yu, Jinyan; Ma, Zhongsen; Shetty, Sreerama; Ma, Mengshi; Fu, Jing

doi:10.1152/ajplung.00051.2016

Cited by 48 publications

(73 citation statements)

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“…α-tubulin is a endogenous substrate of HDAC6 [10, 11, 36–38]. Acetylation of α-tubulin at Lys40 stabilizes microtubule structures [12, 38–41]. The decreased caspase 3 activation by HDAC6 inhibition could be due to its protection against microtubule disassembly by α-tubulin acetylation.…”

Section: Discussionmentioning

confidence: 99%

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HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

et al. 2016

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Pro-inflammatory mediators such as TNF-α induce caspase activation in endothelial cells, which leads to degradation of cellular proteins, induction of apoptotic signaling, and endothelial cell dysfunction. New therapeutic agents that can inhibit caspase activation may provide protection against inflammatory injury to endothelial cells. In the present study, we examined the effects of selective histone deacetylase 6 (HDAC6) inhibition on TNF-α induced caspase 3 activation and cell-cell junction dysfunction in lung endothelial cells. We also assessed the protective effects of HDAC6 inhibition against lung inflammatory injury in a mouse model of endotoxemia. We demonstrated that selective HDAC6 inhibition or knockdown of HDAC6 expression was able to prevent caspase 3 activation in lung endothelial cells and maintain lung endothelial cell-cell junctions. Mice pre-treated with HDAC6 inhibitors exhibited decreased endotoxin-induced caspase 3 activation and reduced lung vascular injury as indicated by the retention of cell-cell junction protein VE-Cadherin level and alleviated lung edema. Collectively, our data suggest that HDAC6 inhibition is a potent therapeutic strategy against inflammatory injury to endothelial cells.

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Section: Discussionmentioning

confidence: 99%

“…HDAC6 siRNA knockdown was conducted as described previously [41]. Cells were transfected with siRNAs for 48 h according to the manufacture's protocol.…”

Section: Methodsmentioning

confidence: 99%

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

et al. 2016

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“…A growing body of evidence suggests that lysine acetylation of β-catenin might also provide an important mechanism for regulating endothelial barrier permeability 227 . Acetylation is a reversible process controlled by acetyltransferases and deacetylases.…”

Section: Signaling Mechanisms Mediating Stability and Remodeling Omentioning

confidence: 99%

“…Knockout of HDAC6 or treatment of animals with the specific HDAC6 inhibitor tubastatin A protects against endotoxin-induced pulmonary edema and acute lung injury and improves survival of mice in septic shock 227, 231 .…”

Section: Signaling Mechanisms Mediating Stability and Remodeling Omentioning

confidence: 99%

Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability

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Mehta

et al. 2017

Circulation Research

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“…As alterações na dinâmica de montagem e desmontagem dos MTs estão associadas ao aumento da fosforilação da cadeia leve da miosina (MLC), que desencadeia alterações nos microfilamentos de actina, causando contração celular (YU et al, 2016).…”

Section: O Endotélio O Citoesqueleto E O Papel Das Rho-gtpasesunclassified

Avaliação do citoesqueleto e da barreira endotelial pulmonar na malária experimental

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Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema

Abstract: Selective HDAC6 inhibition prevents TNF-␣-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema.

Cited by 48 publications

References 55 publications

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions

Protein Interactions at Endothelial Junctions and Signaling Mechanisms Regulating Endothelial Permeability

Avaliação do citoesqueleto e da barreira endotelial pulmonar na malária experimental

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