Pancreatic β Cell-specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes

Hotta, Mizuo; Tashiro, Fumi; Ikegami, Hiroshi; Niwa, Hitoshi; Ogihara, Toshio; Yodoi, Junji; Miyazaki, Jun-ichi

doi:info:doi/10.1084/jem.188.8.1445

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タイトル	Pancreatic β Cell-specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes
著者	Hotta, Mizuo Hotta, Mizuo
	Tashiro, Fumi Tashiro, Fumi
	Ikegami, Hiroshi Ikegami, Hiroshi
	Niwa, Hitoshi Niwa, Hitoshi
	Ogihara, Toshio Ogihara, Toshio
	Yodoi, Junji Yodoi, Junji
	Miyazaki, Jun-ichi Miyazaki, Jun-ichi
キーワード等	oxidative stress
	nonobese diabetic mouse
	insulitis
	cytokine
	apoptosis
抄録	The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in the destruction of pancreatic β cells in insulin-dependent diabetes mellitus (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has recently been shown to protect cells from oxidative stress and apoptosis. To elucidate the roles of oxidative stress in the development of autoimmune diabetes in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in their pancreatic β cells. In these transgenic mice, the incidence of diabetes was markedly reduced, whereas the development of insulitis was not prevented. Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was also attenuated by TRX overexpression in β cells. This is the first direct demonstration that an antioxidative and antiapoptotic protein protects β cells in vivo against both autoimmune and drug-induced diabetes. Our results strongly suggest that oxidative stress plays an essential role in the destruction of β cells by infiltrating inflammatory cells in IDDM.
公開者	The Rockefeller University Press
掲載誌名	Journal of Experimental Medicine
巻	188
号	8
開始ページ	1445
終了ページ	1451
刊行年月	1998-10-19
ISSN	00221007
NCID	AA00697559
DOI	info:doi/10.1084/jem.188.8.1445
URL	http://hdl.handle.net/11094/23106
権利情報	© 1998 Rockefeller University Press
言語	英語
カテゴリ	学術雑誌論文 Journal Article

著者版フラグ	publisher
NII資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
dcmi資源タイプ	text
DCTERMS.bibliographicCitation	Journal of Experimental Medicine.188(8) P.1445-P.1451
DC.title	Pancreatic β Cell-specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes
DC.creator	Hotta, Mizuo
	Tashiro, Fumi
	Ikegami, Hiroshi
	Niwa, Hitoshi
	Ogihara, Toshio
	Yodoi, Junji
	Miyazaki, Jun-ichi
DC.publisher	The Rockefeller University Press
DC.language" scheme="DCTERMS.RFC1766	英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF	1998-10-19
DC.identifier	info:doi/10.1084/jem.188.8.1445
DC.identifier" scheme="DCTERMS.URI	http://hdl.handle.net/11094/23106
DC.subject	oxidative stress
	nonobese diabetic mouse
	insulitis
	cytokine
	apoptosis
DCTERMS.abstract	The cytotoxicity of reactive oxygen intermediates (ROIs) has been implicated in the destruction of pancreatic β cells in insulin-dependent diabetes mellitus (IDDM). Thioredoxin (TRX), a redox (reduction/oxidation)-active protein, has recently been shown to protect cells from oxidative stress and apoptosis. To elucidate the roles of oxidative stress in the development of autoimmune diabetes in vivo, we produced nonobese diabetic transgenic mice that overexpress TRX in their pancreatic β cells. In these transgenic mice, the incidence of diabetes was markedly reduced, whereas the development of insulitis was not prevented. Moreover, induction of diabetes by streptozotocin, an ROI-generating agent, was also attenuated by TRX overexpression in β cells. This is the first direct demonstration that an antioxidative and antiapoptotic protein protects β cells in vivo against both autoimmune and drug-induced diabetes. Our results strongly suggest that oxidative stress plays an essential role in the destruction of β cells by infiltrating inflammatory cells in IDDM.
DC.rights	© 1998 Rockefeller University Press
citation_title	Pancreatic β Cell-specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced Diabetes
citation_author	Hotta, Mizuo
	Tashiro, Fumi
	Ikegami, Hiroshi
	Niwa, Hitoshi
	Ogihara, Toshio
	Yodoi, Junji
	Miyazaki, Jun-ichi
citation_publisher	The Rockefeller University Press
citation_language	英語
citation_date	1998-10-19
citation_journal_title	Journal of Experimental Medicine
citation_volume	188
citation_issue	8
citation_firstpage	1445
citation_lastpage	1451
citation_issn	00221007
citation_doi	info:doi/10.1084/jem.188.8.1445
citation_public_url	http://hdl.handle.net/11094/23106
citation_keywords	oxidative stress
	nonobese diabetic mouse
	insulitis
	cytokine
	apoptosis

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