μ‐Crystallin controls muscle function through thyroid hormone action

Seko, Daiki; Ogawa, Shizuka; Li, Tao‐Sheng; Taimura, Akihiro; Ono, Yusuke

doi:10.1096/fj.15-280933

Cited by 37 publications

(29 citation statements)

References 36 publications

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“…It should be noted that CRAMP1 overexpression levels were the lowest observed for all candidate genes ( Figure S4C). Overexpression of HA-tagged CRYM [73] in Huh7-LP cells resulted in a slight but reproducible increase in replication of the subgenomic HCV replicon after 72 h ( Figure 3D), as well as a notable replication upon infection with the JcR2a reporter virus ( Figure 3F). However, when tagged at the C-terminus with a FLAG-tag, HCV replication was not affected ( Figure 3E), despite substantial overexpression as assessed by qRT-PCR and Western blot ( Figure S4).…”

Section: Crym Lbhd1 and Thap7 Increase Hcv Replication In Lowly Permentioning

confidence: 99%

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Dächert

Gladilin

Binder

2019

Viruses

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Chronic Hepatitis C virus (HCV) infection still constitutes a major global health problem with almost half a million deaths per year. To date, the human hepatoma cell line Huh7 and its derivatives is the only cell line that robustly replicates HCV. However, even different subclones and passages of this single cell line exhibit tremendous differences in HCV replication efficiency. By comparative gene expression profiling using a multi-pronged correlation analysis across eight different Huh7 variants, we identified 34 candidate host factors possibly affecting HCV permissiveness. For seven of the candidates, we could show by knock-down studies their implication in HCV replication. Notably, for at least four of them, we furthermore found that overexpression boosted HCV replication in lowly permissive Huh7 cells, most prominently for the histone-binding transcriptional repressor THAP7 and the nuclear receptor NR0B2. For NR0B2, our results suggest a finely balanced expression optimum reached in highly permissive Huh7 cells, with even higher levels leading to a nearly complete breakdown of HCV replication, likely due to a dysregulation of bile acid and cholesterol metabolism. Our unbiased expression-profiling approach, hence, led to the identification of four host cellular genes that contribute to HCV permissiveness in Huh7 cells. These findings add to an improved understanding of the molecular underpinnings of the strict host cell tropism of HCV.

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Section: Crym Lbhd1 and Thap7 Increase Hcv Replication In Lowly Permentioning

confidence: 99%

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Dächert

Gladilin

Binder

2019

Viruses

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“…For Oil-Red-O staining, Oil-Red-O stock solution [0.6 g Oil Red O (MilliporeSigma, St. Louis, MO, USA) in 100 ml isopropanol] was diluted with water (6:4) and sections incubated with the staining solution at 37°C for 20 min. Immunohistochemistry for fiber types in plantaris (PLA) muscle was performed as previously described (31). Images were acquired with a DP80 camera using cellSens software.…”

Section: Histologic Assessmentmentioning

confidence: 99%

“…Western blot analysis was performed, as previously described (31). Total protein lysates were obtained from muscle tissue after exposure to RIPA buffer (Thermo Fisher Scientific).…”

Section: Western Blottingmentioning

confidence: 99%

Zmynd17 controls muscle mitochondrial quality and whole‐body metabolism

et al. 2018

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Muscle mitochondria are crucial for systemic metabolic function, yet their regulation remains unclear. The zinc finger MYND domain-containing protein 17 (Zmynd17) was recently identified as a muscle-specific gene in mammals. Here, we investigated the role of Zmynd17 in mice. We found Zmynd17 predominantly expressed in skeletal muscle, especially in fast glycolytic muscle. Genetic Zmynd17 inactivation led to morphologic and functional abnormalities in muscle mitochondria, resulting in decreased respiratory function. Metabolic stress induced by a high-fat diet upregulated Zmynd17 expression and further exacerbated muscle mitochondrial morphology in Zmynd17-deficient mice. Strikingly, Zmynd17 deficiency significantly aggravated metabolic stress-induced hepatic steatosis, glucose intolerance, and insulin resistance. Furthermore, middle-aged mice lacking Zmynd17 exhibited impaired aerobic exercise performance, glucose intolerance, and insulin resistance. Thus, our results indicate that Zmynd17 is a metabolic stress-inducible factor that maintains muscle mitochondrial integrity, with its deficiency profoundly affecting whole-body glucose metabolism.-Fujita, R., Yoshioka, K., Seko, D., Suematsu, T., Mitsuhashi, S., Senoo, N., Miura, S., Nishino, I., Ono, Y. Zmynd17 controls muscle mitochondrial quality and whole-body metabolism.

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“…However, CRYM expression is reportedly increased in the skeletal muscle of patients with facioscapulohumeral muscular dystrophy (FSHD), while the expression level is not changed in DMD, polymyositis or limb girdle muscular atrophy . In addition, CRYM knockout mice exhibited a significant hypertrophy of fast‐twitch glycolytic type IIb fibers and gained an increase in grip strength and high intensity running ability . FSHD patients sometimes have deafness or retinopathy complications.…”

Section: Discussionmentioning

confidence: 99%

Expression of CRYM in different rat organs during development and its decreased expression in degenerating pyramidal tracts in amyotrophic lateral sclerosis

et al. 2018

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The protein μ-crystallin (CRYM) is a novel component of the marsupial lens that has two functions: it is a key regulator of thyroid hormone transportation and a reductase of sulfur-containing cyclic ketimines. In this study, we examined changes of the expression pattern of CRYM in different rat organs during development using immunohistochemistry and immunoblotting. As CRYM is reportedly expressed in the corticospinal tract, we also investigated CRYM expression in human cases of amyotrophic lateral sclerosis (ALS) using immunohistochemistry. In the rat brain, CRYM was expressed in the cerebral cortex, basal ganglia, hippocampus and corticospinal tract in the early postnatal period. As postnatal development progressed, CRYM expression was restricted to large pyramidal neurons in layers V and VI of the cerebral cortex and pyramidal cells in the deep layer of CA1 in the hippocampus. Even within the same regions, CRYM-positive and negative neurons were distributed in a mosaic pattern. In the kidney, CRYM was expressed in epithelial cells of the proximal tubule and mesenchymal cells of the medulla in the early postnatal period; however, CRYM expression in the medulla was lost as mesenchymal cell numbers decreased with the rapid growth of the medulla. In human ALS brains, we observed marked loss of CRYM in the corticospinal tract, especially distally. Our results suggest that CRYM may play roles in development of cortical and hippocampal pyramidal cells in the early postnatal period, and in the later period, performs cell-specific functions in selected neuronal populations. In the kidney, CRYM may play roles in maturation of renal function. The expression patterns of CRYM may reflect significance of its interactions with T3 or ketimines in these cells and organs. The results also indicate that CRYM may be used as a marker of axonal degeneration in the corticospinal tract.

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μ‐Crystallin controls muscle function through thyroid hormone action

Cited by 37 publications

References 36 publications

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Gene Expression Profiling of Different Huh7 Variants Reveals Novel Hepatitis C Virus Host Factors

Zmynd17 controls muscle mitochondrial quality and whole‐body metabolism

Expression of CRYM in different rat organs during development and its decreased expression in degenerating pyramidal tracts in amyotrophic lateral sclerosis

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