Search

Your search keyword '"Kusunose, Naoki"' showing total 40 results
Start Over Author "Kusunose, Naoki"
40 results on '"Kusunose, Naoki"'

9. Basis for diurnal exacerbation of neuropathic pain hypersensitivity and its application for drug development.

Author

Koyanagi, Satoru, Kusunose, Naoki, Yasukochi, Sai, and Ohdo, Shigehiro

Subjects
*NEURALGIA, *DRUG development, *DRUG allergy, *CONGESTIVE heart failure, *THERAPEUTICS, *RHINITIS, *HERPESVIRUS diseases
Abstract

In addition to diurnal rhythms in physiology and behavior, a variety of pathological conditions also exhibit marked day–night changes in symptom intensity, exemplified by allergic rhinitis, arthritis, asthma, myocardial infarction, congestive heart failure, stroke and chronic pain disorders. Currently, novel therapeutic approaches are facilitated by the development of chemical compounds targeted to key proteins that cause diurnal exacerbation of pathological events. Neuropathic pain is a chronic condition that occurs by tumor-induced nerve compression, cancer cell infiltration into the nerve, diabetes and herpes virus infection. One troublesome hallmark symptom of neuropathic pain is hypersensitivity to normally innocuous stimuli known as 'mechanical allodynia' that is often refractory to common analgesic therapies. Millions of patients worldwide presently endure neuropathic pain. We summarize the recent insights gained into the mechanism of diurnal exacerbation of neuropathic pain hypersensitivity and introduce the strategy of circadian clock-based drug development. [ABSTRACT FROM AUTHOR]

Published
2022
Full Text
View/download PDF

17. Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain

Author

Tsuda Makoto, Uchida Takahiro, Yoshida Miyako, Matsunaga Naoya, Hamamura Kengo, Koyanagi Satoru, Kusunose Naoki, Inoue Kazuhide, and Ohdo Shigehiro

Subjects
Pathology, RB1-214
Abstract

Abstract Background Neuropathic pain is characterized by hypersensitivity to innocuous stimuli (tactile allodynia) that is nearly always resistant to NSAIDs or even opioids. Gabapentin, a GABA analogue, was originally developed to treat epilepsy. Accumulating clinical evidence supports the effectiveness of this drug for diverse neuropathic pain. In this study, we showed that the anti-allodynic effect of gabapentin was changed by the circadian oscillation in the expression of its target molecule, the calcium channel α2δ-1 subunit. Results Mice were underwent partial sciatic nerve ligation (PSL) to create a model of neuropathic pain. The paw withdrawal threshold (PWT) in PSL mice significantly decreased and fluctuated with a period length about 24 h. The PWT in PSL mice was dose-dependently increased by intraperitoneal injection of gabapentin, but the anti-allodynic effects varied according to its dosing time. The protein levels of α2δ-1 subunit were up-regulated in the DRG of PSL mice, but the protein levels oscillated in a circadian time-dependent manner. The time-dependent oscillation of α2δ-1 subunit protein correlated with fluctuations in the maximal binding capacity of gabapentin. The anti-allodynic effect of gabapentin was attenuated at the times of the day when α2δ-1 subunit protein was abundant. Conclusions These findings suggest that the dosing time-dependent difference in the anti-allodynic effects of gabapentin is attributable to the circadian oscillation of α2δ-1 subunit expression in the DRG and indicate that the optimizing its dosing schedule helps to achieve rational pharmacotherapy for neuropathic pain.

Published
2010
Full Text
View/download PDF

25. Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia

Author

Koyanagi, Satoru, primary, Kusunose, Naoki, additional, Taniguchi, Marie, additional, Akamine, Takahiro, additional, Kanado, Yuki, additional, Ozono, Yui, additional, Masuda, Takahiro, additional, Kohro, Yuta, additional, Matsunaga, Naoya, additional, Tsuda, Makoto, additional, Salter, Michael W., additional, Inoue, Kazuhide, additional, and Ohdo, Shigehiro, additional

Published
2016
Full Text
View/download PDF

32. Time-Dependent Interaction between Differentiated Embryo Chondrocyte-2 and CCAAT/Enhancer-Binding Protein α Underlies the Circadian Expression ofCYP2D6in Serum-Shocked HepG2 Cells

Author

Matsunaga, Naoya, primary, Inoue, Miki, additional, Kusunose, Naoki, additional, Kakimoto, Keisuke, additional, Hamamura, Kengo, additional, Hanada, Yuichi, additional, Toi, Ayumi, additional, Yoshiyama, Yuji, additional, Sato, Fuyuki, additional, Fujimoto, Katsumi, additional, Koyanagi, Satoru, additional, and Ohdo, Shigehiro, additional

Published
2012
Full Text
View/download PDF

36. Modulation of Peroxisome Proliferator-Activated Receptor-αActivity by Bile Acids Causes Circadian Changes in the Intestinal Expression of Octn1/Slc22a4in Mice

Author

Wada, Erika, Koyanagi, Satoru, Kusunose, Naoki, Akamine, Takahiro, Masui, Hiroaki, Hashimoto, Hana, Matsunaga, Naoya, and Ohdo, Shigehiro

Abstract

In addition to their digestive actions, bile acids modulate gene expression by altering the activity of peroxisome proliferator-activated receptor-α(PPARα). The modulatory effects of bile acids have been shown to affect the expression of genes responsible for lipid metabolism as well as membrane transporters. Bile acids are secreted in response to food intake and accumulate in intestinal epithelial cells. In the present study, we identified soluble carrier protein family 22 member 4 (Slc22a4), encoding organic cation transporter novel type-1 (Octn1), as a PPARα-regulated gene and its intestinal expression exhibited circadian oscillations in a bile acid–dependent manner. Nocturnally active mice mainly consumed their food around the early dark phase, during which bile acids accumulated in intestinal epithelial cells. PPARαactivated the intestinal expression of Slc22a4mRNA during the light period, and protein levels of Octn1 peaked before the start of the dark phase. The bile acids that accumulated in intestinal epithelial cells suppressed the PPARα-mediated transactivation of Slc22a4in the dark phase. The time-dependent suppression of PPARα-mediated transactivation by bile acids regulated oscillations in the intestinal expression of Octn1/Slc22a4during the daily feeding cycle. The results of a pharmacokinetic analysis also revealed that oscillations in the expression of Octn1 caused dosing time-dependent differences in the intestinal absorption of gabapentin (2-[1-(aminomethyl)cyclohexyl]acetic acid). These results suggest a molecular clock–independent mechanism by which bile acid–regulated PPARαactivity governs the circadian expression of intestinal organic cation transporters. This mechanism could also account for interindividual variations in the pharmacokinetics of drugs that are substrates of Octn1.

Published
2015
Full Text
View/download PDF

38. Time-Dependent Interaction between Differentiated Embryo Chondrocyte-2 and CCAAT/Enhancer-Binding Protein α Underlies the Circadian Expression of CYP2D6 in Serum-Shocked HepG2 Cells

Author

Matsunaga, Naoya, Inoue, Miki, Kusunose, Naoki, Kakimoto, Keisuke, Hamamura, Kengo, Hanada, Yuichi, Toi, Ayumi, Yoshiyama, Yuji, Sato, Fuyuki, Fujimoto, Katsumi, Koyanagi, Satoru, and Ohdo, Shigehiro

Abstract

Differentiated embryo chondrocyte-2 (DEC2), also known as bHLHE41 or Sharp1, is a pleiotropic transcription repressor that controls the expression of genes involved in cellular differentiation, hypoxia responses, apoptosis, and circadian rhythm regulation. Although a previous study demonstrated that DEC2 participates in the circadian control of hepatic metabolism by regulating the expression of cytochrome P450, the molecular mechanism is not fully understood. We reported previously that brief exposure of HepG2 cells to 50% serum resulted in 24-h oscillation in the expression of CYP3A4 as well as circadian clock genes. In this study, we found that the expression of CYP2D6, a major drug-metabolizing enzyme in humans, also exhibited a significant oscillation in serum-shocked HepG2 cells. DEC2 interacted with CCAAT/enhancer-binding protein (C/EBPα), accompanied by formation of a complex with histone deacetylase-1, which suppressed the transcriptional activity of C/EBPα to induce the expression of CYP2D6. The oscillation in the protein levels of DEC2 in serum-shocked HepG2 cells was nearly antiphase to that in the mRNA levels of CYP2D6. Transfection of cells with small interfering RNA against DEC2 decreased the amplitude of CYP2D6 mRNA oscillation in serum-shocked cells. These results suggest that DEC2 periodically represses the promoter activity of CYP2D6, resulting in its circadian expression in serum-shocked cells. DEC2 seems to constitute a molecular link through which output components from the circadian clock are associated with the time-dependent expression of hepatic drug-metabolizing enzyme.

Published
2012

39. Suppression of neuropathic pain in the circadian clock-deficient Per2 m/m mice involves up-regulation of endocannabinoid system.

Author

Yamakawa W, Yasukochi S, Tsurudome Y, Kusunose N, Yamaguchi Y, Tsuruta A, Matsunaga N, Ushijima K, Koyanagi S, and Ohdo S

Abstract

Neuropathic pain often results from injuries and diseases that affect the somatosensory system. Disruption of the circadian clock has been implicated in the exacerbation of the neuropathic pain state. However, in this study, we report that mice deficient in a core clock component Period2 ( Per2 m/m mice) fail to develop tactile pain hypersensitivity even following peripheral nerve injury. Similar to male wild-type mice, partial sciatic nerve ligation (PSL)- Per2 m/m male mice showed activation of glial cells in the dorsal horn of the spinal cord and increased expression of pain-related genes. Interestingly, α1D-adrenergic receptor (α1D-AR) expression was up-regulated in the spinal cord of Per2 m/m mice, leading to increased production of 2-arachidonoylglycerol (2-AG), an endocannabinoid receptor ligand. This increase in 2-AG suppressed the PSL-induced tactile pain hypersensitivity. Furthermore, intraspinal dorsal horn injection of adeno-associated viral vectors expressing α1D-AR also attenuated pain hypersensitivity in PSL-wild-type male mice by increasing 2-AG production. Our findings reveal an uncovered role of the circadian clock in neuropathic pain disorders and suggest a link between α1D-AR signaling and the endocannabinoid system., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Published
2024
Full Text
View/download PDF

40. Modulation of peroxisome proliferator-activated receptor-α activity by bile acids causes circadian changes in the intestinal expression of Octn1/Slc22a4 in mice.

Author

Wada E, Koyanagi S, Kusunose N, Akamine T, Masui H, Hashimoto H, Matsunaga N, and Ohdo S

Subjects
Animals, Caco-2 Cells, Circadian Rhythm drug effects, Humans, Intestinal Mucosa drug effects, Male, Mice, Mice, Inbred ICR, Mice, Knockout, Organic Cation Transport Proteins, Symporters, Bile Acids and Salts pharmacology, Carrier Proteins biosynthesis, Circadian Rhythm physiology, Gene Expression Regulation, Intestinal Mucosa metabolism, Membrane Proteins biosynthesis, PPAR alpha metabolism
Abstract

In addition to their digestive actions, bile acids modulate gene expression by altering the activity of peroxisome proliferator-activated receptor-α (PPARα). The modulatory effects of bile acids have been shown to affect the expression of genes responsible for lipid metabolism as well as membrane transporters. Bile acids are secreted in response to food intake and accumulate in intestinal epithelial cells. In the present study, we identified soluble carrier protein family 22 member 4 (Slc22a4), encoding organic cation transporter novel type-1 (Octn1), as a PPARα-regulated gene and its intestinal expression exhibited circadian oscillations in a bile acid-dependent manner. Nocturnally active mice mainly consumed their food around the early dark phase, during which bile acids accumulated in intestinal epithelial cells. PPARα activated the intestinal expression of Slc22a4 mRNA during the light period, and protein levels of Octn1 peaked before the start of the dark phase. The bile acids that accumulated in intestinal epithelial cells suppressed the PPARα-mediated transactivation of Slc22a4 in the dark phase. The time-dependent suppression of PPARα-mediated transactivation by bile acids regulated oscillations in the intestinal expression of Octn1/Slc22a4 during the daily feeding cycle. The results of a pharmacokinetic analysis also revealed that oscillations in the expression of Octn1 caused dosing time-dependent differences in the intestinal absorption of gabapentin (2-[1-(aminomethyl)cyclohexyl]acetic acid). These results suggest a molecular clock-independent mechanism by which bile acid-regulated PPARα activity governs the circadian expression of intestinal organic cation transporters. This mechanism could also account for interindividual variations in the pharmacokinetics of drugs that are substrates of Octn1., (Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.)

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results