HECT‐Type Ubiquitin E3 Ligase ITCH Interacts With Thioredoxin‐Interacting Protein and Ameliorates Reactive Oxygen Species–Induced Cardiotoxicity

Otaki, Yoichiro; Takahashi, Hitomi; Watanabe, Tetsu; Funayama, Akira; Netsu, Shunsuke; Honda, Yuki; Narumi, Takatsune; Kadowaki, Shinpei; Hasegawa, Hiromasa; Honda, Shintaro; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Kamata, Hideaki; Nakajima, Osamu

doi:10.1161/jaha.115.002485

Cited by 36 publications

(22 citation statements)

References 45 publications

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“…Isolation and culture of neonatal rat cardiomyocytes (NRCMs) were performed as we previously described [21]. Briefly, ventricles were obtained from 1-to 2-day-old Sprague-Dawley rat pups (mixed gender) after euthanasia by decapitation, and cardiomyocytes were isolated by digestion with collagenase.…”

Section: Neonatal Rat Cardiomyocyte Isolation Cell Culture and Treamentioning

confidence: 99%

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The association between microRNA-21 and hypertension-induced cardiac remodeling

et al. 2020

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Hypertension is a major public health problem among the aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its contribution to cardiac remodeling in hypertension is poorly understood. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-β1 (TGF-β1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-β1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic stimulation-induced cardiac remodeling by regulating PDCD4, AP-1, and TGF-β1 signaling pathway.

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Section: Neonatal Rat Cardiomyocyte Isolation Cell Culture and Treamentioning

confidence: 99%

“…The total protein extracts were prepared with radio-immunoprecipitation assay (RIPA) buffer as we previously reported [21]. Equal amounts of protein were subjected to 10% SDS-PAGE and transferred to polyvinylidene difluoride membranes.…”

Section: Western Blottingmentioning

confidence: 99%

The association between microRNA-21 and hypertension-induced cardiac remodeling

et al. 2020

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“…ITCH increases proteasomal TXNIP degradation and augments thioredoxin activity, leading to inhibition of ROS generation, p38 MAPK, and p53, improvement of oxidative stress response in ROS-induced cardiotoxicity, and improvement of survival in ROSinduced cardiotoxicity and myocardial infarction. [96] WWP1 also belongs to the E3 ubiquitinated ligase HECT family. It has been reported that WWP1 can degrade p53 through the ubiquitin-proteasome pathway.…”

Section: Journal Of Translational Internal Medicine / Apr-jun 2020 / mentioning

confidence: 99%

Structure and function of HECT E3 ubiquitin ligases and their role in oxidative stress

Hao

Zhang

et al. 2020

Journal of Translational Internal Medicine

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Ubiquitination is a modification after protein transcription that plays a vital role in maintaining the homeostasis of the cellular environment. The Homologous to E6AP C-terminus (HECT) family E3 ubiquitin ligases are a kind of E3 ubiquitin ligases with a C-terminal HECT domain that mediates the binding of ubiquitin to substrate proteins and a variable-length N-terminal extension. HECT-ubiquitinated ligases can be divided into three categories: NEDD4 superfamily, HERC superfamily, and other HECT superfamilies. HECT ubiquitin ligase plays an essential role in the development of many human diseases. In this review, we focus on the physiological and pathological processes involved in oxidative stress and the role of E3 ubiquitin ligase of the HECT family.

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“…Moreover, iTcH plays an important role in regulating apoptosis and other biological processes (19). it has also been shown that in myocardial cells, Txnip is a target protein of ubiquitin molecules (20). By interacting with e3 ligase-iTcH, Txnip protein expression is degraded by ubiquitin, thus reversing the degree of myocardial cell apoptosis caused by myocardial infarction (20).…”

Section: Introductionmentioning

confidence: 99%

ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells

et al. 2020

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Thioredoxin (Trx) is an important protein that controls oxidative damage in almost all eukaryotic cells. Trx interaction protein (Txnip) has been reported to negatively regulate the bioavailability of Trx and inhibit its biological function. The e3 ubiquitin ligase iTcH can specifically degrade Txnip via ubiquitination. The apoptosis of human lens epithelial cells (Hlecs), which are highly sensitive to redox caused by oxidative stress, is a significant factor for the development of sugar cataract in a high-glucose environment. However, whether Trx, Txnip and iTcH contribute to the progression of sugar cataracts and the underlying mechanisms remain unknown, and thus, identifying these were the aims of the present study. The present results suggested that the expression levels of Trx, Txnip and iTcH in Hlecs cultured with different glucose concentrations were detected by reverse transcription-quantitative Pcr and western blotting, and the apoptotic rate of the cells was detected by flow cytometry and superoxide detection assay. The interaction between iTcH and Txnip was determined by co-localization immunofluorescence and co-immunoprecipitation. in addition, a vector and small interfering rna of iTcH were transfected to overexpress and knockdown iTcH, respectively, to alter the expression of downstream proteins and cell apoptosis. it was found that Txnip was highly expressed in cultured Hlecs in high-glucose environment, and the antioxidative function of Trx was restricted and suppressed, thus promoting apoptosis. The overexpression of iTcH increased the expression of Trx and decreased oxidative stress and apoptosis by decreasing Txnip in cultured Hlecs, while downregulation of iTcH significantly decreased the expression of Trx and enhanced oxidative stress and apoptosis. Therefore, the present results indicated that iTcH could regulate the apoptosis of Hlecs that were cultured in high-glucose concentration and that it may be a treatment target for sugar cataract.

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HECT‐Type Ubiquitin E3 Ligase ITCH Interacts With Thioredoxin‐Interacting Protein and Ameliorates Reactive Oxygen Species–Induced Cardiotoxicity

Cited by 36 publications

References 45 publications

The association between microRNA-21 and hypertension-induced cardiac remodeling

The association between microRNA-21 and hypertension-induced cardiac remodeling

Structure and function of HECT E3 ubiquitin ligases and their role in oxidative stress

ITCH regulates oxidative stress induced by high glucose through thioredoxin interacting protein in cultured human lens epithelial cells

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