The Keap1-Nrf2 System Prevents Onset of Diabetes Mellitus

REFERENCES

• Itoh K, Igarashi K, Hayashi N, Nishizawa M, Yamamoto M. 1995. Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins. Mol. Cell. Biol. 15:4184–4193.
   PubMed Web of Science ®Google Scholar
• Moi P, Chan K, Asunis I, Cao A, Kan YW. 1994. Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc. Natl. Acad. Sci. U. S. A. 91:9926–9930.
   PubMed Web of Science ®Google Scholar
• Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M. 1999. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 13:76–86.
   PubMed Web of Science ®Google Scholar
• Cullinan SB, Gordan JD, Jin J, Harper JW, Diehl JA. 2004. The Keap1-BTB protein is an adaptor that bridges Nrf2 to a Cul3-based E3 ligase: oxidative stress sensing by a Cul3-Keap1 ligase. Mol. Cell. Biol. 24:8477–8486.
   PubMed Web of Science ®Google Scholar
• Furukawa M, Xiong Y. 2005. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the cullin 3-Roc1 ligase. Mol. Cell. Biol. 25:162–171.
   PubMed Web of Science ®Google Scholar
• Kobayashi A, Kang MI, Okawa H, Ohtsuji M, Zenke Y, Chiba T, Igarashi K, Yamamoto M. 2004. Oxidative stress sensor Keap1 functions as an adaptor for Cul3-based E3 ligase to regulate proteasomal degradation of Nrf2. Mol. Cell. Biol. 24:7130–7139.
   PubMed Web of Science ®Google Scholar
• Ishii T, Itoh K, Takahashi S, Sato H, Yanagawa T, Katoh Y, Bannai S, Yamamoto M. 2000. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J. Biol. Chem. 275:16023–16029.
   PubMed Web of Science ®Google Scholar
• Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y. 1997. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236:313–322.
   PubMed Web of Science ®Google Scholar
• Kobayashi M, Li L, Iwamoto N, Nakajima-Takagi Y, Kaneko H, Nakayama Y, Eguchi M, Wada Y, Kumagai Y, Yamamoto M. 2009. The antioxidant defense system Keap1-Nrf2 comprises a multiple sensing mechanism for responding to a wide range of chemical compounds. Mol. Cell. Biol. 29:493–502.
   PubMed Web of Science ®Google Scholar
• Uruno A, Motohashi H. 2011. The Keap1-Nrf2 system as an in vivo sensor for electrophiles. Nitric Oxide 25:153–160.
   PubMedGoogle Scholar
• Taguchi K, Motohashi H, Yamamoto M. 2011. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 16:123–140.
   PubMed Web of Science ®Google Scholar
• Yoh K, Hirayama A, Ishizaki K, Yamada A, Takeuchi M, Yamagishi S, Morito N, Nakano T, Ojima M, Shimohata H, Itoh K, Takahashi S, Yamamoto M. 2008. Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice. Genes Cells 13:1159–1170.
   PubMed Web of Science ®Google Scholar
• Aleksunes LM, Reisman SA, Yeager RL, Goedken MJ, Klaassen CD. 2010. Nuclear factor erythroid 2-related factor 2 deletion impairs glucose tolerance and exacerbates hyperglycemia in type 1 diabetic mice. J. Pharmacol. Exp. Ther. 333:140–151.
   PubMed Web of Science ®Google Scholar
• Shin S, Wakabayashi J, Yates MS, Wakabayashi N, Dolan PM, Aja S, Liby KT, Sporn MB, Yamamoto M, Kensler TW. 2009. Role of Nrf2 in prevention of high-fat diet-induced obesity by synthetic triterpenoid CDDO-imidazolide. Eur. J. Pharmacol. 620:138–144.
   PubMed Web of Science ®Google Scholar
• Shin S, Wakabayashi N, Misra V, Biswal S, Lee GH, Agoston ES, Yamamoto M, Kensler TW. 2007. NRF2 modulates aryl hydrocarbon receptor signaling: influence on adipogenesis. Mol. Cell. Biol. 27:7188–7197.
   PubMed Web of Science ®Google Scholar
• Mitsuishi Y, Taguchi K, Kawatani Y, Shibata T, Nukiwa T, Aburatani H, Yamamoto M, Motohashi H. 2012. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 22:66–79.
   PubMed Web of Science ®Google Scholar
• Taguchi K, Maher JM, Suzuki T, Kawatani Y, Motohashi H, Yamamoto M. 2010. Genetic analysis of cytoprotective functions supported by graded expression of Keap1. Mol. Cell. Biol. 30:3016–3026.
   PubMed Web of Science ®Google Scholar
• Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S, Takahashi S, Imakado S, Kotsuji T, Otsuka F, Roop DR, Harada T, Engel JD, Yamamoto M. 2003. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet. 35:238–245.
   PubMed Web of Science ®Google Scholar
• Azhar M, Wang PY, Frugier T, Koishi K, Deng C, Noakes PG, McLennan IS. 2010. Myocardial deletion of Smad4 using a novel α skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract. Int. J. Biol. Sci. 6:546–555.
   PubMedGoogle Scholar
• Noguchi N, Yoshikawa T, Ikeda T, Takahashi I, Shervani NJ, Uruno A, Yamauchi A, Nata K, Takasawa S, Okamoto H, Sugawara A. 2008. FKBP12.6 disruption impairs glucose-induced insulin secretion. Biochem. Biophys. Res. Commun. 371:735–740.
   PubMedGoogle Scholar
• Abramoff M, Magalhaes P, Ram S. 2004. Image processing with ImageJ. Biophotonics Int. 11:36–42.
   Google Scholar
• Uruno A, Matsuda K, Noguchi N, Yoshikawa T, Kudo M, Satoh F, Rainey WE, Hui XG, Akahira J, Nakamura Y, Sasano H, Okamoto H, Ito S, Sugawara A. 2011. Peroxisome proliferator-activated receptor-γ suppresses CYP11B2 expression and aldosterone production. J. Mol. Endocrinol. 46:37–49.
   PubMedGoogle Scholar
• Uruno A, Noguchi N, Matsuda K, Nata K, Yoshikawa T, Chikamatsu Y, Kagechika H, Harigae H, Ito S, Okamoto H, Sugawara A. 2011. All-trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL-60 cells: possible involvement of protein kinase C-δ. J. Leukoc. Biol. 90:235–247.
   PubMed Web of Science ®Google Scholar
• Uruno A, Sugawara A, Kanatsuka H, Kagechika H, Saito A, Sato K, Kudo M, Takeuchi K, Ito S. 2005. Upregulation of nitric oxide production in vascular endothelial cells by all-trans retinoic acid through the phosphoinositide 3-kinase/Akt pathway. Circulation 112:727–736.
   PubMedGoogle Scholar
• McMahon M, Itoh K, Yamamoto M, Chanas SA, Henderson CJ, McLellan LI, Wolf CR, Cavin C, Hayes JD. 2001. The Cap‘n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes. Cancer Res. 61:3299–3307.
   PubMed Web of Science ®Google Scholar
• Proulx K, Cota D, Castañeda TR, Tschöp MH, D'Alessio DA, Tso P, Woods SC, Seeley RJ. 2005. Mechanisms of oleoylethanolamide-induced changes in feeding behavior and motor activity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289:R729–R737.
   PubMed Web of Science ®Google Scholar
• Yadav R, Gupta SC, Hillman BG, Bhatt JM, Stairs DJ, Dravid SM. 2012. Deletion of glutamate delta-1 receptor in mouse leads to aberrant emotional and social behaviors. PLoS One 7:e32969. doi:10.1371/journal.pone.0032969.
   PubMed Web of Science ®Google Scholar
• Pei L, Waki H, Vaitheesvaran B, Wilpitz DC, Kurland IJ, Tontonoz P. 2006. NR4A orphan nuclear receptors are transcriptional regulators of hepatic glucose metabolism. Nat. Med. 12:1048–1055.
   PubMed Web of Science ®Google Scholar
• Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM. 2001. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413:131–138.
   PubMed Web of Science ®Google Scholar
• Conkright MD, Guzmán E, Flechner L, Su AI, Hogenesch JB, Montminy M. 2003. Genome-wide analysis of CREB target genes reveals a core promoter requirement for cAMP responsiveness. Mol. Cell 11:1101–1108.
   PubMed Web of Science ®Google Scholar
• Liby KT, Sporn MB. 2012. Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease. Pharmacol. Rev. 64:972–1003.
   PubMed Web of Science ®Google Scholar
• Song MY, Kim EK, Moon WS, Park JW, Kim HJ, So HS, Park R, Kwon KB, Park BH. 2009. Sulforaphane protects against cytokine- and streptozotocin-induced β-cell damage by suppressing the NF-κB pathway. Toxicol. Appl. Pharmacol. 235:57–67.
   PubMed Web of Science ®Google Scholar
• Saha PK, Reddy VT, Konopleva M, Andreeff M, Chan L. 2010. The triterpenoid 2-cyano-3,12-dioxooleana-1,9-dien-28-oic-acid methyl ester has potent anti-diabetic effects in diet-induced diabetic mice and Lepr(db/db) mice. J. Biol. Chem. 285:40581–40592.
   PubMed Web of Science ®Google Scholar
• Pergola PE, Raskin P, Toto RD, Meyer CJ, Huff JW, Grossman EB, Krauth M, Ruiz S, Audhya P, Christ-Schmidt H, Wittes J, Warnock DG, BEAM Study Investigators. 2011. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N. Engl. J. Med. 365:327–336.
   PubMed Web of Science ®Google Scholar
• Meher AK, Sharma PR, Lira VA, Yamamoto M, Kensler TW, Yan Z, Leitinger N. 2012. Nrf2 deficiency in myeloid cells is not sufficient to protect mice from high-fat diet-induced adipose tissue inflammation and insulin resistance. Free Radic. Biol. Med. 52:1708–1715.
   PubMed Web of Science ®Google Scholar
• Ahmad R, Raina D, Meyer C, Kharbanda S, Kufe D. 2006. Triterpenoid CDDO-Me blocks the NF-κB pathway by direct inhibition of IKKβ on Cys-179. J. Biol. Chem. 281:35764–35769.
   PubMed Web of Science ®Google Scholar
• Ahmad R, Raina D, Meyer C, Kufe D. 2008. Triterpenoid CDDO-methyl ester inhibits the Janus-activated kinase-1 (JAK1)→signal transducer and activator of transcription-3 (STAT3) pathway by direct inhibition of JAK1 and STAT3. Cancer Res. 68:2920–2926.
   PubMedGoogle Scholar
• Wang Y, Porter WW, Suh N, Honda T, Gribble GW, Leesnitzer LM, Plunket KD, Mangelsdorf DJ, Blanchard SG, Willson TM, Sporn MB. 2000. A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor γ. Mol. Endocrinol. 14:1550–1556.
   PubMed Web of Science ®Google Scholar
• Handschin C, Spiegelman BM. 2008. The role of exercise and PGC1α in inflammation and chronic disease. Nature 454:463–469.
   PubMed Web of Science ®Google Scholar
• Lin J, Handschin C, Spiegelman BM. 2005. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 1:361–370.
   PubMed Web of Science ®Google Scholar
• Cho HY, Jedlicka AE, Reddy SP, Zhang LY, Kensler TW, Kleeberger SR. 2002. Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate gene. Am. J. Respir. Cell Mol. Biol. 26:42–51.
   PubMed Web of Science ®Google Scholar
• Yamamoto T, Yoh K, Kobayashi A, Ishii Y, Kure S, Koyama A, Sakamoto T, Sekizawa K, Motohashi H, Yamamoto M. 2004. Identification of polymorphisms in the promoter region of the human NRF2 gene. Biochem. Biophys. Res. Commun. 321:72–79.
   PubMed Web of Science ®Google Scholar
• Marzec JM, Christie JD, Reddy SP, Jedlicka AE, Vuong H, Lanken PN, Aplenc R, Yamamoto T, Yamamoto M, Cho HY, Kleeberger SR. 2007. Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. FASEB J. 21:2237–2246.
   PubMed Web of Science ®Google Scholar
• Safdar A, deBeer J, Tarnopolsky MA. 2010. Dysfunctional Nrf2-Keap1 redox signaling in skeletal muscle of the sedentary old. Free Radic. Biol. Med. 49:1487–1493.
   PubMed Web of Science ®Google Scholar
• Kensler TW, Wakabayashi N. 2010. Nrf2: friend or foe for chemoprevention? Carcinogenesis 31:90–99.
   PubMed Web of Science ®Google Scholar