1999 Fiscal Year Final Research Report Summary
Effect of glucose and cytokines on apoptosis of vascular smooth muscle cells
| Project/Area Number |
09671083
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内分泌・代謝学
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| Research Institution | Aichi Medical University |
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Principal Investigator |
SAKAKIBARA Fumihiko Aichi Medical University, First Department of Internal Medicine, Instructor, 医学部, 講師 (60273231)
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| Co-Investigator(Kenkyū-buntansha) |
YAMANOUCHI Kunio Aichi Medical University, First Department of Internal Medicine, Associate Professor, 医学部, 助教授 (60135366)
KUSUNOKI Masataka Aichi Medical University, First Department of Internal Medicine, Instructor, 医学部, 講師 (80214956)
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| Project Period (FY) |
1997 – 1999
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| Keywords | apoptosis / atherosclerosis / glucose / INF -γ / IL-1β / TNF-α / cytokine / diabetes |
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| Research Abstract |
We investigated whether glucose and cytokines can trigger apoptosis of VSMC of rabbit aorta. VSMC were cultured for <72 hours in DMEM containing 5.5 or 55 mM glucose with INF -γ(400 U/mL), IL-1β (100 U/mL), and TNF-α (400 U/mL), each or together. DNA fragments, as an evidence of apoptosis, were detected in situ by using TUNEL method. Quantification of nuclear labeling was performed by counting the percentage of TUNEL-positive cells. No significant difference between 5.5 and 55 mM glucose of percentage of apoptotic cell was observed. With 5.5 mM glucose in the presence of INF -γ, IL-1β and TNF-α each alone percentage of apoptotic cell did not increased significantly (<4%). However, 29.4±6.9% of VSMC in the cultures cotreated with 3 cytokines for 72 hours showed positive staining with TUNEL(p<0.05 versus untreated with cytokines). With 55 mM glucose the same tendency of results was harvested. Increase VSMC proliferation under hyperglycemia has already been reported. Although these cytokines indeces apoptosis, hyperglycemia does not increase the induction of apoptosis cooperatively with cytokines. Since hyperglycema does not promote the apoptosis but proliferation of VSMC, diabetes may often cause progression of atherosclerosis.
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[Publications] Kusunoki M, Hara T, Tsutsumi K, Nakamura T, Miyata T, Sakakibara F, Sakamoto S, Ogawa H, Nakaya Y, Storlien LH.: "The lipoprotein lipase activator, NO-1886, suppresses fat accumulation and insulin resistance in rats fed a high-fat diet."Diabetologia. 43. 875-80 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] Nakamura J, Kato K, Hamada Y, Nakayama M, Chaya S, Nakashima E, Naruse K, Kasuya Y, Mizubayashi R, Miwa K, Yasuda Y, Kamiya H, Ienaga K, Sakakibara F, Koh N, Hotta N.: "A protein kinase C-beta-selective inhibitor ameliorates neural dysfunction in streptozotocin-induced diabetic rats."Diabetes. 48. 2090-5 (1999)
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[Publications] Sasaki H, Nakamura J, Koh N, Hamada Y, Hara T, Chaya S, Nakashima E, Naruse K, Kato K, Kasuya Y, Sakakibara F, Hotta N.: "Effect of vitamin E and allylamine on the proliferation of cultured aortic smooth muscle cells from streptozotocin-induced diabetic rats."Life Sci. 64. 2317-25 (1999)
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[Publications] Nakamura J, Koh N, Sakakibara F, Hamada Y, Hara T, Sasaki H, Chaya S, Komori T, Nakashima E, Naruse K, Kato K, Takeuchi N, Kasuya Y, Hotta N.: "Polyol pathway hyperactivity is closely related to carnitine deficiency in the pathogenesis of diabetic neuropathy of streptozotocin-diabetic rats."J Pharmacol Exp Ther. 287. 897-902 (1999)
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[Publications] Hotta N, Nakamura J, Sakakibara F, Hamada Y, Hara T, Mori K, Nakashima E, Sasaki H, Kasama N, Inukai S, Koh N.: "Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant."Am J Physiol. 273. E965-71 (1997)
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[Publications] Mori K, Nakamura J, Koh N, Sakakibara F, Hamada Y, Hara T, Komori T, Nakashima E, Naruse K, Takeuchi N, Hotta N.: "Increased alanine uptake and lipid synthesis from alanine in isolated hepatocytes of Wistar-Kyoto fatty rats : an inhibitory effect of biguanides."Can J Physiol Pharmacol. 75. 179-84 (1997)
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[Publications] Nakamura J, Koh N, Sakakibara F, Hamada Y, Wakao T, Sasaki H, Mori K, Nakashima E, Naruse K, Hotta N.: "Diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats : effect of an aldose reductase inhibitor, TAT."Life Sci. 60. 1847-57 (1997)
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