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Molecular Basis of Familial Glucocorticoid Deficiency

Research Project

Project/Area Number 26461542
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

山口 理恵  浜松医科大学, 医学部, 特任研究員 (50420360)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Discontinued (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsFGD / NNT deficiency / oxidative stress / mitochodria / bioenergetics / ATP / MAPK pathway / NNT activity / patient / lymphocyte / mitochondria / NNT / ROS / cortisol / redox status / HAC15 cells
Outline of Annual Research Achievements

The objectives of this project are 1) to verify NNT defect impairs cellular redox status and mitochondrial bioenergetics both in vitro and in vivo; 2) to validate the impaired cellular redox status mediates MAPK pathways to inhibit mitochondrial ATP production and induce apoptosis and subsequent decreased cellular viability; 3) to identify new genes responsible for FGD and elucidate the underlying mechanism(s)
The following results were obtained.
1. NNT knockdown resulted in an oxidized cellular redox status and impaired mitochondrial bioenergetics in HAC15 cells (a human adrenocortical cell line)
2. The FGD patient with NNT deficiency showed higher ROS production rate in the lymphocytic mitochondria, suggesting NNT deficiency lead to increased oxidative stress in the patient.
3. The effect of NNT deficiency on mitochondrial bioenergetics in the FGD patient was not performed due to lack of blood sample and all the remaining experiments were stopped due to the researcher’s retirement.

Report

(3 results)
  • 2016 Annual Research Report
  • 2015 Research-status Report
  • 2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-01-16  

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