No Amelioration of Uromodulin Maturation and Trafficking Defect by Sodium 4-Phenylbutyrate in Vivo

Kemter, Elisabeth; Sklenak, Stefanie; Rathkolb, Birgit; Angelis, Martin Hrabé de; Wolf, Eckhard; Aigner, Bernhard; Wanke, Rüdiger

doi:10.1074/jbc.m113.537035

Cited by 23 publications

(23 citation statements)

References 42 publications

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“…To date, reports on the effect of 4-PBA on other HSPs have been mixed. 4-PBA induced mRNA expression of HSP60 in a murine macrophage cell line (46); however, 4-PBA did not induce changes in HSP70 expression in COS-7 cells, primary epithelial cells, or mouse models of kidney disease (47)(48)(49). Although in the current study we observed a tendency toward 4-PBAinduced expression of HSP70 in THP-1 macrophages, such induction was not statistically significant, and neither was HSP90 expression.…”

Section: Discussioncontrasting

confidence: 73%

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice

et al. 2019

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Endoplasmic reticulum stress plays an important role in cardiovascular disease (CVD) and atherosclerosis. We aimed to assess the ability of 4‐phenylbutyrate (4‐PBA), a small chemical chaperone administered via drinking water, to reduce atherosclerotic lesion size in chow‐fed apolipoprotein (Apo) e−/− mice and to identify mechanisms that contribute to its antiatherogenic effect. Chow‐fed 17‐wk‐old female Apoe−/− mice treated with 4‐PBA–supplemented drinking water for 5 wk exhibited smaller lesions as well as increased plasma levels of heat shock protein (HSP) 25, the mouse homolog of human HSP27, compared with controls. In addition, 4‐PBA inhibited cell death and increased HSP27 expression as measured by real‐time PCR and immunoblotting, as well as induced nuclear localization of its transcription factor, heat shock factor 1, in human monocyte/macrophage (THP‐1) cells. Furthermore, HSP27 small interfering RNA diminished the protective effect of 4‐PBA on THP‐1 macrophage attachment and differentiation. In summary, drinking water containing 4‐PBA attenuated early lesion growth in Apoe−/− mice fed a chow diet and increased expression of HSP25 and HSP27 in macrophages and HSP25 in the circulation of Apoe−/− mice. Given that increased expression of HSP27 is inversely correlated with CVD risk, our findings suggest that 4‐PBA protects against the early stages of atherogenesis in part by enhancing HSP27 levels, leading to inhibition of both macrophage cell death and monocyte‐macrophage differentiation.—Lynn, E. G., Lhoták, Š., Lebeau, P., Byun, J. H., Chen, J., Platko, K., Shi, C., O'Brien, E. R., Austin, R. C. 4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe−/− mice. FASEB J. 33, 8406–8422 (2019). http://www.fasebj.org

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Section: Discussioncontrasting

confidence: 73%

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice

et al. 2019

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“…The chemical chaperone sodium 4-phenylbutyrate (4-PBA) improves folding and maturation of mutant uromodulin in in-vitro studies, suggesting that UAKD is caused by ER stress [13,14]. Wanke and colleagues reported that the nuclear factor kappa B (NF-kB) pathway was activated in the thick ascending limb of Henle's loop cells of UAKD mice, suggesting that NF-kB is a novel therapeutic target of UAKD, although 4-PBA caused a deterioration kidney function of UAKD mice [15].…”

Section: Endoplasmic Reticulum Stress Evoked By Genetic Mutation Of Rmentioning

confidence: 96%

Endoplasmic reticulum stress in kidney function and disease

Taniguchi

Yoshida

2015

Current Opinion in Nephrology and Hypertension

115

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“…Recently, contrasting in vivo evidence about the effects of 4-PBA on UAKD in vivo has become available. A study found that though 4-PBA was associated with similar beneficial effects in vitro, administration in an animal model was unable to prevent renal damage in mice with mutations which cause UAKD (Kemter et al, 2014).…”

Section: The Effects Of 4-pba On Protein Misfolding Diseases -Geneticmentioning

confidence: 97%

The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis

Kolb

Ayaub

Zhou

et al. 2015

The International Journal of Biochemistry & Cell Biology

222

182

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No Amelioration of Uromodulin Maturation and Trafficking Defect by Sodium 4-Phenylbutyrate in Vivo

Cited by 23 publications

References 42 publications

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice

Endoplasmic reticulum stress in kidney function and disease

The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis

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No Amelioration of Uromodulin Maturation and Trafficking Defect by Sodium 4-Phenylbutyrate in Vivo

Cited by 23 publications

References 42 publications

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe −/− mice

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe −/− mice

Endoplasmic reticulum stress in kidney function and disease

The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis

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Product

Resources

About

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice

4‐Phenylbutyrate protects against atherosclerotic lesion growth by increasing the expression of HSP25 in macrophages and in the circulation of Apoe ^−/− mice