092-642-6612

092-642-6614

Ph.D

No

Chronopharmacology, Chronopharmaceutics（chrono-DDS）,Chrono drug discovery,　Microcurrent therapy of molecular clock

00years00months

Research Interests

• Microcurrent therapy of circadina clock
  keyword : Microcurrent therapy circadina clock
  2017.04～2027.10.
• Drug discovery of anti-cancer and anti-inflammatory based on circadian machinery
  keyword : chrono-drug discovery
  2018.03～2018.03.
• Study on proper use for medicine of which it is basic is biological rhythm
  
  New DDS development of which it is basic is biological rhythm
  keyword : chronopharmacology 　chronotherapy
  1998.04.

Academic Activities Awards

• A molecular clock mechanism of cytochrome P450 (CYP) genes expression in serum-shocked HepG2 cells
  [Objective(s)]
  Circadian rhythms have been observed in many biological systems and physiological functions. The effectiveness and toxicity of many drugs vary depending on the dosage in association with 24-hr rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. Although the pharmacokinetics of several drugs, which are mainly eliminated by cytochrome P450 (CYP) metabolism, vary according to their dosing time, mechanism of the variation remains poorly understood. In this study, we investigated how the 24 hr oscillation in the expression of CYP was generated in hepatic cells.
  
  [Materials and Methods]
  As brief exposure of HepG2 cells to 50% serum induced the 24 hr oscillation in the expression of clock genes, serum-shocked HepG2 cells were used as an in vitro model to study the molecular mechanism underlying the circadian clock in human liver. The amount of protein and mRNA were measured by Western blot analysis and RT-PCR. CYP- promoter activity was measured by Dual-Luciferase assay
  
  [Results and Discussion]
  The present study suggests that temporal variations of CYPs expression were controlled by the transcriptional level in cultured human hepatocyte. Transcription of the CYP promoter was rhythmically controlled by clock genes. Our present findings provide a molecular link between the circadian clock and xenobiotic metabolism. In addition, these cultured cell models may be useful in the analysis of the molecular clock mechanism of the human biological rhythm research.
  
• Circadian rhythms have been observed in many biological systems and physiological functions. The effectiveness and toxicity of many drugs vary depending on the dosing time, associated with 24-hr rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. Recently, several clock genes have been identified, and they control an array of circadian rhythms in physiology and behavior. According to the currently held model, the core circadian oscillator consists of an autoregulatory transcription-translation feedback loop (Fig). CLOCK and BMAL1 proteins form a heterodimer and then activate the transcription of Per and Cry genes. Once PER and CRY proteins have reached a critical concentration, they attenuate CLOCK:BMAL1-mediated activation of their own genes in a negative feedback loop.
  Time-dependent changes in pharmacokinetics proceed from 24 hr rhythms in　each process, e.g. absorption, distribution, metabolism　and elimination. Since the liver　is a major organ of metabolism and detoxifcation,　knowledge of circadian effects on transcriptional　activities that govern daily biochemical and physiological　processes in the liver may play a key role in toxicology. In mouse liver, circadian regulation of transcripts is demonstrated for the factor of phase I, II of drug metabolism such as Cyp17, Cyp2a4, Cyp2e1, Cyp2c22, Cyp3a, glutathione S-transferases (GST) and carboxylesterase so on. In the recent our study, the transactivation of the human CYP3a4 gene by DBP is repressed by the E4 promoter-binding protein-4 (E4BP4), a negative component of the circadian clock (Fig).1) On the other hand, hepatocyte nuclear factor-1 alpha (HNF-1α) and clock genes contribute to produce the 24-hr rhythm of CYP2e1 mRNA levels in mouse liver.2)
  

Other Educational Activities

• 2019.04.
• 2018.04.
• 2017.04.
• 2016.10.
• 2015.12.
• 2014.12.
• 2013.12.
• 2012.12.
• 2011.12.
• 2010.12.
• 2009.12.
• 2008.12.