Molecular mechanisms of disturbance in cell survival system by alcohol abuse
| Project/Area Number |
16390196
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
MATSUMOTO Hiroshi Sapporo Medical University, School of Medicine, Professor (60263092)
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| Co-Investigator(Kenkyū-buntansha) |
NISHITANI Yoko Sapporo Medical University, School of Medicine, Instructor (30359997)
FUJII Kenichi Sapporo Medical University, School of Medicine, Instructor (60419661)
IMABAYASHI Kiyomi Sapporo Medical University, School of Medicine, Instructor (50419660)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥13,100,000 (Direct Cost: ¥13,100,000)
Fiscal Year 2005: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥9,400,000 (Direct Cost: ¥9,400,000)
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| Keywords | alcohol / NF-kappaB / JNK / Akt / SREBP / TLR4 / polyunsaturated fatty acid / NAFLD / CYP2E1 / PPAR / NF-KappaB / SREBP |
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| Research Abstract |
1. Activations of JNK and Akt were enhanced by co-treatment with ethanol and a classical inhibitor of alcohol dehydrogenase (ADH). Addition of an anti- oxidant reduced the activation of JNK. Ethanol loading with ADH inhibition causes down-regulation of GRP78 mRNA levels. Therefore, these findings suggest first revelation that inhibition of ethanol metabolism complicates oxidative and ER stresses produced by ethanol..
2. The development of nonalcoholic fatty liver was not associated with insulin resistance but involves suppression of SREBP-1c. This suggests an activator of SREBP-1c may induce the progression of steatosis to steatohepatitis. Since NF- κB inhibitors reduced the steatosis as well as PPAR agonists and then decreased endoplasmic reticulum stress, they may be also effective in ameliorating NAFLD.
3. Fish oil feeding caused inflammation in the liver and induced proinflammatory cytokines, PPARs, CYP4As, and CYP2E1. Fish oil contains rich polyunsaturated fatty acids. These findings suggest that polyunsaturated fatty acid plays a crucial role in development of alcoholic and nonalcoholic fatty liver disease.
4. Hindlimb unloading caused elevating portal endotoxin levels, but did not cause sever liver injury. Acute ethanol treatment for the hindlimb unloading model induced disturbance in proinflammmatory response via TLR4 signalling.
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Report
(3 results)
Research Products
(32 results)
