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        Arginine Supplementation Recovered the IFN-γ-Mediated Decrease in Milk Protein and Fat Synthesis by Inhibiting the GCN2/eIF2α Pathway, Which Induces Autophagy in Primary Bovine Mammary Epithelial Cells

        Xia, Xiaojing,Che, Yanyi,Gao, Yuanyuan,Zhao, Shuang,Ao, Changjin,Yang, Hongjian,Liu, Juxiong,Liu, Guowen,Han, Wenyu,Wang, Yuping,Lei, Liancheng Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.5

        During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mechanism. Interferon gamma ($IFN-{\gamma}$) is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines in vitro. However, it remains unclear whether $IFN-{\gamma}$ can induce autophagy and whether autophagy affects milk synthesis in BMECs. To understand whether $IFN-{\gamma}$ affects milk synthesis, we isolated and purified primary BMECs and investigated the effect of $IFN-{\gamma}$ on milk synthesis in primary BMECs in vitro. The results showed that $IFN-{\gamma}$ significantly inhibits milk synthesis and that autophagy was clearly induced in primary BMECs in vitro within 24 h. Interestingly, autophagy was observed following $IFN-{\gamma}$ treatment, and the inhibition of autophagy can improve milk protein and milk fat synthesis. Conversely, upregulation of autophagy decreased milk synthesis. Furthermore, mechanistic analysis confirmed that $IFN-{\gamma}$ mediated autophagy by depleting arginine and inhibiting the general control nonderepressible-2 kinase (GCN2)/eukaryotic initiation factor $2{\alpha}$ ($eIF2{\alpha}$) signaling pathway in BMECs. Then, it was found that arginine supplementation could attenuate $IFN-{\gamma}$-induced autophagy and recover milk synthesis to some extent. These findings may not only provide a novel measure for preventing the $IFN-{\gamma}$-induced decrease in milk quality but also a useful therapeutic approach for $IFN-{\gamma}$-associated breast diseases in other animals and humans.

      • KCI등재

        Complete Genome of Leptospirillum ferriphilum ML-04 Provides Insight into Its Physiology and Environmental Adaptation

        Shuang Mi,Jian Song,Yuanyuan Che,Huajun Zheng,Jianqiang Lin,Jianqun Lin 한국미생물학회 2011 The journal of microbiology Vol.49 No.6

        Leptospirillum ferriphilum has been identified as the dominant, moderately thermophilic, bioleaching microorganism in bioleaching processes. It is an acidic and chemolithoautrophic bacterium that gains electrons from ferrous iron oxidation for energy production and cell growth. Genetic information about this microorganism has been limited until now, which has hindered its further exploration. In this study, the complete genome of L. ferripilum ML-04 is sequenced and annotated. The bacterium has a single circular chromosome of 2,406,157 bp containing 2,471 coding sequences (CDS), 2 rRNA operons, 48 tRNA genes, a large number of mobile genetic elements and 2 genomic islands. In silico analysis shows L. ferriphilum ML-04 fixes carbon through a reductive citric acid (rTCA) cycle, and obtains nitrogen through ammonium assimilation. The genes related to “cell envelope biogenesis, outer membrane” (6.9%) and “DNA replication, recombination and repair” (5.6%) are abundant, and a large number of genes related to heavy metal detoxification, oxidative and acidic stress defense, and signal transduction pathways were detected. The genomic plasticity, plentiful cell envelope components, inorganic element metabolic abilities and stress response mechanisms found the base for this organism’s survival in the bioleaching niche.

      • KCI등재

        Arginine Supplementation Recovered the IFN-gamma-Mediated Decrease in Milk Protein and Fat Synthesis by Inhibiting the GCN2/eIF2alpha Pathway, Which Induces Autophagy in Primary Bovine Mammary Epithelial Cells

        Liancheng Lei,Xiaojing Xia,Yanyi Che,Yuanyuan Gao,Shuang Zhao,Changjin Ao,Hongjian Yang,Juxiong Liu,Guo-wen Liu,Wenyu Han,Yuping Wang 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.5

        During the lactation cycle of the bovine mammary gland, autophagy is induced in bovine mammary epithelial cells (BMECs) as a cellular homeostasis and survival mecha-nism. Interferon gamma (IFN-) is an important antiproliferative and apoptogenic factor that has been shown to induce autophagy in multiple cell lines in vitro. However, it remains unclear whether IFN- can induce autophagy and whether autophagy affects milk synthesis in BMECs. To understand whether IFN- affects milk synthesis, we isolated and purified primary BMECs and investigated the effect of IFN- on milk synthesis in primary BMECs in vitro. The results showed that IFN- significantly inhibits milk synthesis and that autophagy was clearly induced in primary BMECs in vitro within 24 h. Interestingly, autophagy was observed following IFN- treatment, and the inhibition of autophagy can improve milk protein and milk fat syn-thesis. Conversely, upregulation of autophagy decreased milk synthesis. Furthermore, mechanistic analysis con-firmed that IFN- mediated autophagy by depleting argi-nine and inhibiting the general control nonderepressible-2 kinase (GCN2)/eukaryotic initiation factor 2 (eIF2) signaling pathway in BMECs. Then, it was found that arginine supplementation could attenuate IFN--induced autophagy and recover milk synthesis to some extent. These findings may not only provide a novel measure for preventing the IFN--induced decrease in milk quality but also a useful therapeutic approach for IFN--associated breast diseases in other animals and humans.

      • KCI등재

        piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination

        Zhang Wentao,Zheng Zongtai,Wang Keyi,Mao Weipu,Li Xue,Wang Guangchun,Zhang Yuanyuan,Huang Jianhua,Zhang Ning,Wu Pengfei,Liu Ji,Zhang Haimin,Che Jianping,Peng Bo,Zheng Junhua,Li Wei,Yao Xudong 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

        Accumulating studies have confirmed that PIWI-interacting RNAs (piRNAs) are considered epigenetic effectors in cancer. We performed piRNA microarray expression analysis on renal cell carcinoma (RCC) tumor tissues and paired normal tissues and performed a series of in vivo and in vitro experiments to explore piRNAs associated with RCC progression and investigate their functional mechanisms. We found that piR-1742 was highly expressed in RCC tumors and that patients with high piR-1742 expression had a poor prognosis. Inhibition of piR-1742 significantly reduced tumor growth in RCC xenograft and organoid models. Mechanistically, piRNA-1742 regulates the stability of USP8 mRNA by binding directly to hnRNPU, which acts as a deubiquitinating enzyme that inhibits the ubiquitination of MUC12 and promotes the development of malignant RCC. Subsequently, nanotherapeutic systems loaded with piRNA-1742 inhibitors were found to effectively inhibit the metastasis and growth of RCC in vivo. Therefore, this study highlights the functional importance of piRNA-related ubiquitination in RCC and demonstrates the development of a related nanotherapeutic system, possibly contributing to the development of therapeutic approaches for RCC.

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