Endoplasmic reticulum stress mediates aristolochic acid I-induced apoptosis in human renal proximal tubular epithelial cells

Zhu, Shuguang; Wang, Yan; Jin, Jing; Guan, Cuiwen; Li, Mei; Chen, Xi; Ouyang, Zizhang; Chen, Meiwan; Qiu, Yudong; Huang, Min; Huang, Zhiying

doi:10.1016/j.tiv.2012.03.005

Cited by 44 publications

(32 citation statements)

References 39 publications

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“…Cells were treated with 4-PBA (0.1~1 mM) and TGF-β (5 ng/ml; R&D Systems, Minneapolis, MN, USA) in 0.1 or 0.5% FBS-added medium at the indicated dosages and time points. The selection of 4-PBA concentration was based on the previous study and our preliminary experiments [45]. …”

Section: Methodsmentioning

confidence: 99%

Chemical chaperon 4-phenylbutyrate protects against the endoplasmic reticulum stress-mediated renal fibrosisin vivoandin vitro

et al. 2016

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Renal tubulointerstitial fibrosis is the common and final pathologic change of kidney in end-stage renal disease. Interesting, endoplasmic reticulum (ER) stress is known to contribute to the pathophysiological mechanisms during the development of renal fibrosis. Here, we investigated the effects of chemical chaperon sodium 4-phenylbutyrate (4-PBA) on renal fibrosis in vivo and in vitro. In a rat unilateral ureteral obstruction (UUO) model, 4-PBA mimicked endogenous ER chaperon in the kidneys and significantly reduced glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), activating transcription factor 4 (ATF4), and phosphorylated JNK protein expressions as well as restored spliced X-box-binding protein 1 (XBP1) expressions in the kidneys of UUO rats. 4-PBA also attenuated the increases of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF) protein expressions, tubulointerstitial fibrosis, and apoptosis in the kidneys of UUO rats. Moreover, transforming growth factor (TGF)-β markedly increased ER stress-associated molecules, profibrotic factors, and apoptotic markers in the renal tubular cells (NRK-52E), all of which could be significantly counteracted by 4-PBA treatment. 4-PBA also diminished TGF-β-increased CTGF promoter activity and CTGF mRNA expression in NRK-52E cells. Taken together, our results indicated that 4-PBA acts as an ER chaperone to ameliorate ER stress-induced renal tubular cell apoptosis and renal fibrosis.

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Section: Methodsmentioning

confidence: 99%

Chemical chaperon 4-phenylbutyrate protects against the endoplasmic reticulum stress-mediated renal fibrosisin vivoandin vitro

et al. 2016

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“…AAI-induced apoptosis leads to the development of human interstitial nephropathy and eventually acute renal failure or end-stage renal disease. Zhu et al (2012) found that 4-PBA is able to reduce activation of caspase-3 and decrease cell death, a vital step in understanding the nephrotoxicity behind AAI. In Sawada et al's (2008) paper, bladder-derived smooth muscle cells were exposed to CoCl 2 or thenoyltrifluoroacetone, this caused GRP78 and CHOP levels to become elevated via hypoxia-related pathways.…”

Section: The Use Of 4-pba In Diseases Related To Metabolic Syndrome Amentioning

confidence: 99%

The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis

Kolb

Ayaub

Zhou

et al. 2015

The International Journal of Biochemistry & Cell Biology

215

182

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“…The cDNAs were PCR amplified using specific primers for XBP1 (Zhu et al 2012), CCAAT/enhancerbinding protein homologous protein (CHOP) (Wang et al 2011), and glucose-regulated protein 78 kDa (GRP78) (Lin et al 2012). The primers used were XBP1F (5′-GGTAAGGAACTGGGTCCTT-3′) and XBP1R (5′-GAGTTAAGACAGCGCTTGGG-3′).…”

Section: Dna Fragmentation Assaymentioning

confidence: 99%

Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling

Sharma

Kaur

Bhatnagar

et al. 2015

Cell Stress and Chaperones

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The acidic microenvironment around tumor cells is a major determinant in cancer growth, metabolism, and metastasis. However, its role in cancer physiology is still not clearly understood. In the present investigation, an attempt has been made to explore the effect of acidic environment on physiology of cancer cells. Exposure of Raji cells to extracellular acidic environment was associated with enhanced cytosolic calcium level and endoplasmic reticulum stress response. X-box binding protein 1 (XBP1) splicing, CCAAT/ enhancer-binding protein homologous protein (CHOP), and glucose-regulated protein 78 kDa (GRP78) upregulation suggested endoplasmic reticulum stress generation. On the other hand, real-time-based upregulation of Bax gene expression and flow cytometric analysis of cytochrome c release as well as enhanced active caspase-3 further confirmed mitochondrion-mediated events leading to induction of apoptosis. The expression of TP53 and p21 was upregulated. These observations collectively strongly suggest that both endoplasmic reticulum stress-mediated calcium release and Bax targeting might be altering mitochondrion membrane potential which in turn could induce secondary apoptotic signals; subsequently, endoplasmic reticulum stress can also lead to nuclear localization of Nuclear factor-κB (NF-κB) which in turn favors p53 mediated apoptotic signals.

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Endoplasmic reticulum stress mediates aristolochic acid I-induced apoptosis in human renal proximal tubular epithelial cells

Cited by 44 publications

References 39 publications

Chemical chaperon 4-phenylbutyrate protects against the endoplasmic reticulum stress-mediated renal fibrosisin vivoandin vitro

Chemical chaperon 4-phenylbutyrate protects against the endoplasmic reticulum stress-mediated renal fibrosisin vivoandin vitro

The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis

Low-pH-induced apoptosis: role of endoplasmic reticulum stress-induced calcium permeability and mitochondria-dependent signaling

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