Heat shock protein 90 is a new potential target of anti-rejection therapy in allotransplantation

Maehana, Takeshi; Tanaka, Toshiaki; Hashimoto, Kohei; Kobayashi, Ko; Kitamura, Hiroshi; Masumori, Naoya

doi:10.1007/s12192-022-01272-2

Cited by 2 publications

(1 citation statement)

References 46 publications

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“… 23 , 33 They act via the suppression of activated Hsp90, a molecular chaperone in charge with protein stability. 34 Interestingly, global UPR modulation due to Brefeldin A and Kifunensine affected endothelial cytoskeletal remodeling by cofilin and myosin light chain 2 (MLC2) activation regulation. 35 , 36 Cofilin is phosphorylated by Rac1 and severs actin filaments, whereas MLC2 activation signals filamentous actin formation.…”

Section: Discussionmentioning

confidence: 99%

Unfolded protein response suppression potentiates LPS-induced barrier dysfunction and inflammation in bovine pulmonary artery endothelial cells

Barabutis

Akhter

2023

Tissue Barriers

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The development of novel strategies to counteract diseases related to barrier dysfunction is a priority, since sepsis and acute respiratory distress syndrome are still associated with high mortality rates. In the present study, we focus on the effects of the unfolded protein response suppressor (UPR) 4-Phenylbutyrate (4-PBA) in Lipopolysaccharides (LPS)-induced endothelial injury, to investigate the effects of that compound in the corresponding damage. 4-PBA suppressed binding immunoglobulin protein (BiP) – a UPR activation marker – and potentiated LPS – induced signal transducer and activator of transcription 3 (STAT3) and extracellular signal‑regulated protein kinase (ERK) 1/2 activation. In addition to those effects, 4-PBA enhanced paracellular hyperpermeability in inflamed bovine pulmonary endothelial cells, and did not affect cell viability in moderate concentrations. Our observations suggest that UPR suppression due to 4-PBA augments LPS-induced endothelial injury, as well as the corresponding barrier disruption.

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