Browsing by Author "Yin, Jiye"

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    In vitro and in vivo inhibition of the host TRPC4 channel attenuates Zika virus infection
    (EMBO Press, 2024) Chen, Xingjuan; Yan, Yunzheng; Liu, Zhiqiang; Yang, Shaokang; Li, Wei; Wang, Zhuang; Wang, Mengyuan; Guo, Juan; Li, Zhenyang; Zhu, Weiyan; Yang, Jingjing; Yin, Jiye; Dai, Qingsong; Li, Yuexiang; Wang, Cui; Zhao, Lei; Yang, Xiaotong; Guo, Xiaojia; Leng, Ling; Xu, Jiaxi; Obukhov, Alexander G.; Cao, Ruiyuan; Zhong, Wu; Anatomy, Cell Biology and Physiology, School of Medicine
    Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.
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    Multidrug resistance-associated protein 1 (MRP1/ABCC1) polymorphism: from discovery to clinical application
    (Wanfang Med Online, 2011-10) Yin, Jiye; Zhang, Jianting; Department of Pharmacology and Toxicology, IU School of Medicine
    Multidrug resistance-associated protein 1 (MRP1/ABCC1) is the first identified member of ABCC subfamily which belongs to ATP-binding cassette (ABC) transporter superfamily. It is ubiquitously expressed in almost all human tissues and transports a wide spectrum of substrates including drugs, heavy metal anions, toxicants, and conjugates of glutathione, glucuronide and sulfate. With the advance of sequence technology, many MRP1/ABCC1 polymorphisms have been identified. Accumulating evidences show that some polymorphisms are significantly associated with drug resistance and disease susceptibility. In vitro reconstitution studies have also unveiled the mechanism for some polymorphisms. In this review, we present recent advances in understanding the role and mechanism of MRP1/ABCC1 polymorphisms in drug resistance, toxicity, disease susceptibility and severity, prognosis prediction, and methods to select and predict functional polymorphisms.