Redox-dependent and independent effects of thioredoxin interacting protein
BIOLOGICAL CHEMISTRY
Authors: Cao, Xiankun; He, Wenxin; Pang, Yichuan; Cao, Yu; Qin, An
Abstract
Thioredoxin interacting protein (TXNIP) is an important physiological inhibitor of the thioredoxin (TXN) redox system in cells. Regulation of TXNIP expression and/or activity not only plays an important role in redox regulation but also exerts redox-independent physiological effects that exhibit direct pathophysiological consequences including elevated inflammatory response, aberrant glucose metabolism, cellular senescence and apoptosis, cellular immunity, and tumorigenesis. This review provides a brief overview of the current knowledge concerning the redox-dependent and independent roles of TXNIP and its relevance to various disease states. The implications for the therapeutic targeting of TXNIP will also be discussed.
ASC-deficiency impairs host defense against Aeromonas hydrophila infection in Japanese medaka, Oryzias latipes
FISH & SHELLFISH IMMUNOLOGY
Authors: Morimoto, Natsuki; Okamura, Yo; Maekawa, Shun; Wang, Han-Ching; Aoki, Takashi; Kono, Tomoya; Sakai, Masahiro; Hikima, Jun-ichi
Abstract
Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) is a component of inflammasome, which plays crucial roles in the inflammatory response. In mammals, ASC regulates caspase-1 activation, thereby inducing pyroptosis and producing activated inflammatory cytokines. In addition, ASC also interacts with receptor-interacting protein kinase 2 (RIPK2) and induces nuclear factor-kappa B (NF-kappa B) activation. However, the role of ASC remains poorly understood in fish. In this study, we focused on elucidating the role of ASC in fish that were infected with Aeromonas hydrophila using Japanese medaka (Oryzias latipes) as fish model, and ASC-knockout (KO) medaka was established using CRISPR-Cas9 system. ASC-KO and wild type (WT) medakas were infected with A. hydrophila, and mortality was observed. ASC-KO medaka demonstrated higher mortality than WT. Moreover, the expression of immune-related genes in the kidney and intestine of the ASC-KO and WT medakas challenged with A. hydrophila were analyzed. Following A. hydrophila infection, the kidney of ASC-KO medaka exhibited significantly lower expression of NF-kappa B regulated genes (e.g., IL-1 beta, IL-6, IL-8 and TNF-alpha) and RIPK2 gene than in WT kidney. Moreover, to investigate the immune response against A. hydrophila via ASC in the medaka, bacterial burden, superoxide anion production, and lactate dehydmgenase release in the kidney cells of ASC-KO medaka were measured. After infection, these responses in ASC-KO medaka were significantly decreased compared to those in WT. These results suggest that the medaka ASC plays a critical role against A. hydrophila infection by inducing inflammatory responses and cell death for bacterial clearance.