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Gene Review

Nfkbia  -  nuclear factor of kappa light polypeptide...

Rattus norvegicus

Synonyms: I-kappa-B-alpha, IkB-alpha, IkappaBalpha, Ikba, NF-kappa-B inhibitor alpha, ...
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Disease relevance of Nfkbia

  • We conclude that diet-induced obesity and acute HL reduce IkappaBalpha levels in rat skeletal muscle in a fiber-type-dependent manner [1].
  • CONCLUSIONS: Inhibition of nuclear translocation of NF-kappaB by IkappaBalpha phosphorylation blockade could provide an effective approach to attenuation of ischemia/reperfusion injury [2].
  • IkappaBalpha degradation, NF-kappaB activation, and iNOS expression were attenuated by parthenolide (3mg/kg), the active constituent of feverfew, an anti-inflammatory drug used for migraine treatment [3].
  • However, hypoxia could not prevent either degradation of an inhibitory protein (IkappaBalpha) of nuclear factor-kappaB (NF-kappaB) or translocation of NF-kappaB to the nucleus, whereas heat inhibited both of the IkappaBalpha degradation and NF-kappaB translocation [4].
  • Blocking of NF-kappaB activation in cytokine-exposed primary beta-cells by an adenovirus overexpressing a nondegradable form of IkappaBalpha or by pyrrolidine dithiocarbamate decreased IL-1beta-induced MCP-1 mRNA expression [5].

High impact information on Nfkbia


Chemical compound and disease context of Nfkbia

  • Transient nuclear factor kappaB (NF-kappaB) activation stimulated by interleukin-1beta may be partly dependent on proteasome activity, but not phosphorylation and ubiquitination of the IkappaBalpha molecule, in C6 glioma cells. Regulation of NF-kappaB linked to chemokine production [10].
  • Superfusion of the in-situ brain with N(alpha)-L-tosyl-L-phenylalanine chloromethyl ketone (TPCK), a specific inhibitor of IKB-alpha proteolysis, attenuated greatly the spasmogenic, leukocyte rolling-endothelial cell adhesion and postcapillary hemorrhages induced by ethanol [11].
  • Hyperoxia reduced nuclear factor kappaB activation in the heart during sustained ischemia and reperfusion and increased the cytoplasmatic inhibitory factor IkappaBalpha [12].
  • Finally, we analysed the effect of the inhibition of IkappaBalpha degradation on glutamate-induced toxicity by using BAY 11-7082, a selective inhibitor of IkappaBalpha phosphorylation [13].
  • The inhibition of NFkappaB observed in rats preconditioned with 3 min ischemia, KA5 or LIN500 treatments compared with ischemic or epileptic controls was correlated with the prevention of the inducible degradation of the inhibitory protein IkappaBalpha [14].

Biological context of Nfkbia

  • Taken together, these data suggest that basal IkappaBalpha expression (and as a consequence NF-kappaB activity) is under the control of the various components of the CBF1/Notch signal transduction pathway [15].
  • PTX and wortmannin, a PI3 K inhibitor, not only inhibited the PDGF-activated phosphorylation of Akt but also suppressed p70(S6 K) expression and IkappaBalpha degradation, inhibiting nuclear translocation and the DNA binding activity of NF-kappaB [16].
  • In addition to CD14, rapid increases in gene expression of IkappaBalpha, IL-1beta, and TNF-alpha occurred along the meninges and ventricular ependyma [17].
  • Furthermore 'in vitro' IRFI 042 (50 microM) significantly inhibited activation of NF-kappaB through inhibition of IkappaBalpha degradation, reduced the amount of TNF-alpha mRNA, decreased LPS-induced TNF-alpha release and blunted lipid peroxidation (MAL) in LPS stimulated Mphi [18].
  • The effect of rapamycin appeared to be independent of the phosphatidylinositol 3-kinase/Akt-protein kinase B survival pathway, because the phosphatidylinositol 3-kinase inhibitor wortmannin neither prevented IkappaBalpha degradation nor increased apoptosis of cells incubated with TNF-alpha [19].

Anatomical context of Nfkbia


Associations of Nfkbia with chemical compounds

  • Importantly, the fiber-type-dependent effects on IkappaBalpha levels could not be explained by differential accumulation of triglyceride in Sol and Vas [1].
  • Activation of nuclear factor kappaB and Bcl-x survival gene expression by nerve growth factor requires tyrosine phosphorylation of IkappaBalpha [9].
  • IRFI-042, a vitamin E analogue (20 mg/kg intraperitoneally 2 min after the end of bleeding), inhibited the loss of IkappaBalpha protein from the cytoplasm and blunted the increase in NF-kappaB binding activity [25].
  • LPS shocked rats also had increased TNF-alpha mRNA levels, augmented liver NF-kappaB binding activity in the nucleus and decreased levels of the inhibitory protein IkappaBalpha [18].
  • Cyclosporin inhibited the loss of IkappaBalpha protein from the cytoplasm and prevented NF-kappaB binding activity in the nucleus [26].

Physical interactions of Nfkbia

  • The level of Nuclear Factor (kappa) inhibitor (IkappaBalpha) in liver was decreased and DNA-binding activity of Nuclear Factor-kappaB (NF-kappaB) was increased after thermal injury. p38 MAP kinase was more significantly activated in liver harvested from burn rats than from shams [27].

Regulatory relationships of Nfkbia


Other interactions of Nfkbia

  • In the brain parenchyma, increased TLR4 immunoreactivity was confined to the vasculature and neighboring tissues along with strong vascular expression of IkappaBalpha and mPGES-1 [17].
  • HYP content in liver, the expressions of ICAM-1, VCAM-1 mRNA and protein, NF-kappaBp65 and alpha-SMA protein were decreased significantly and IkappaBalpha protein in liver was elevated significantly in this group [32].
  • Basal expression of IkappaBalpha is controlled by the mammalian transcriptional repressor RBP-J (CBF1) and its activator Notch1 [15].
  • SNAP also blocked cytokine- induced increase in NF-kappaB activation, iNOS promoter activity, nuclear translocation of cytosolic NF-kappaB p65 subunit, and IkappaBalpha degradation, which correlated with its inhibitory effect on phosphorylation and ubiquitination of IkappaB [33].
  • Ang II treatment also resulted in the degradation of IkappaBalpha and increase of NF-kappaB p65 subunit in the nucleus as well as the DNA binding activity of nuclear NF-kappaB [34].

Analytical, diagnostic and therapeutic context of Nfkbia


  1. Diet-induced obesity and acute hyperlipidemia reduce IkappaBalpha levels in rat skeletal muscle in a fiber-type dependent manner. Bhatt, B.A., Dube, J.J., Dedousis, N., Reider, J.A., O'Doherty, R.M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  2. Inhibition of IkappaB phosphorylation in cardiomyocytes attenuates myocardial ischemia/reperfusion injury. Onai, Y., Suzuki, J., Kakuta, T., Maejima, Y., Haraguchi, G., Fukasawa, H., Muto, S., Itai, A., Isobe, M. Cardiovasc. Res. (2004) [Pubmed]
  3. Nuclear factor-kappaB as a molecular target for migraine therapy. Reuter, U., Chiarugi, A., Bolay, H., Moskowitz, M.A. Ann. Neurol. (2002) [Pubmed]
  4. Hypoxia and heat inhibit inducible nitric oxide synthase gene expression by different mechanisms in rat hepatocytes. Inoue, T., Kwon, A.H., Oda, M., Kaibori, M., Kamiyama, Y., Nishizawa, M., Ito, S., Okumura, T. Hepatology (2000) [Pubmed]
  5. Molecular regulation of monocyte chemoattractant protein-1 expression in pancreatic beta-cells. Kutlu, B., Darville, M.I., Cardozo, A.K., Eizirik, D.L. Diabetes (2003) [Pubmed]
  6. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Digicaylioglu, M., Lipton, S.A. Nature (2001) [Pubmed]
  7. Regulation by C5a of neutrophil activation during sepsis. Riedemann, N.C., Guo, R.F., Bernacki, K.D., Reuben, J.S., Laudes, I.J., Neff, T.A., Gao, H., Speyer, C., Sarma, V.J., Zetoune, F.S., Ward, P.A. Immunity (2003) [Pubmed]
  8. NFkappaB prevents apoptosis and liver dysfunction during liver regeneration. Iimuro, Y., Nishiura, T., Hellerbrand, C., Behrns, K.E., Schoonhoven, R., Grisham, J.W., Brenner, D.A. J. Clin. Invest. (1998) [Pubmed]
  9. Activation of nuclear factor kappaB and Bcl-x survival gene expression by nerve growth factor requires tyrosine phosphorylation of IkappaBalpha. Bui, N.T., Livolsi, A., Peyron, J.F., Prehn, J.H. J. Cell Biol. (2001) [Pubmed]
  10. Transient nuclear factor kappaB (NF-kappaB) activation stimulated by interleukin-1beta may be partly dependent on proteasome activity, but not phosphorylation and ubiquitination of the IkappaBalpha molecule, in C6 glioma cells. Regulation of NF-kappaB linked to chemokine production. Uehara, T., Matsuno, J., Kaneko, M., Nishiya, T., Fujimuro, M., Yokosawa, H., Nomura, Y. J. Biol. Chem. (1999) [Pubmed]
  11. Inhibitor of nuclear factor-Kappa B activation attenuates venular constriction, leukocyte rolling-adhesion and microvessel rupture induced by ethanol in intact rat brain microcirculation: relation to ethanol-induced brain injury. Altura, B.M., Gebrewold, A. Neurosci. Lett. (2002) [Pubmed]
  12. Hyperoxia elicits myocardial protection through a nuclear factor kappaB-dependent mechanism in the rat heart. Tähepõld, P., Vaage, J., Starkopf, J., Valen, G. J. Thorac. Cardiovasc. Surg. (2003) [Pubmed]
  13. Inhibition of IkappaBalpha phosphorylation prevents glutamate-induced NF-kappaB activation and neuronal cell death. Pizzi, M., Sarnico, I., Boroni, F., Benetti, A., Benarese, M., Spano, P.F. Acta Neurochir. Suppl. (2005) [Pubmed]
  14. Activation of the nuclear factor-kappaB is a key event in brain tolerance. Blondeau, N., Widmann, C., Lazdunski, M., Heurteaux, C. J. Neurosci. (2001) [Pubmed]
  15. Basal expression of IkappaBalpha is controlled by the mammalian transcriptional repressor RBP-J (CBF1) and its activator Notch1. Oakley, F., Mann, J., Ruddell, R.G., Pickford, J., Weinmaster, G., Mann, D.A. J. Biol. Chem. (2003) [Pubmed]
  16. Blocking of Akt/NF-{kappa}B Signaling by Pentoxifylline Inhibits Platelet-Derived Growth Factor-Stimulated Proliferation in Brown Norway Rat Airway Smooth Muscle Cells. Chiou, Y.L., Shieh, J.J., Lin, C.Y. Pediatr. Res. (2006) [Pubmed]
  17. Differential expression of the CD14/TLR4 complex and inflammatory signaling molecules following i.c.v. administration of LPS. Xia, Y., Yamagata, K., Krukoff, T.L. Brain Res. (2006) [Pubmed]
  18. Inhibition of nuclear factor-kappaB activation by IRFI 042, protects against endotoxin-induced shock. Altavilla, D., Squadrito, G., Minutoli, L., Deodato, B., Bova, A., Sardella, A., Seminara, P., Passaniti, M., Urna, G., Venuti, S.F., Caputi, A.P., Squadrito, F. Cardiovasc. Res. (2002) [Pubmed]
  19. Rapamycin antagonizes NF-kappaB nuclear translocation activated by TNF-alpha in primary vascular smooth muscle cells and enhances apoptosis. Giordano, A., Avellino, R., Ferraro, P., Romano, S., Corcione, N., Romano, M.F. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  20. Lentiviral-mediated Targeted NF-kappaB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat. Meunier, A., Latrémolière, A., Dominguez, E., Mauborgne, A., Philippe, S., Hamon, M., Mallet, J., Benoliel, J.J., Pohl, M. Mol. Ther. (2007) [Pubmed]
  21. Selective activation of the c-Jun N-terminal kinase (JNK) pathway fails to elicit Bax activation or apoptosis unless the phosphoinositide 3'-kinase (PI3K) pathway is inhibited. Molton, S.A., Todd, D.E., Cook, S.J. Oncogene (2003) [Pubmed]
  22. Induction of transcriptional activity of AP-1 and NF-kappaB in the gastric mucosa during aging. Xiao, Z.Q., Majumdar, A.P. Am. J. Physiol. Gastrointest. Liver Physiol. (2000) [Pubmed]
  23. Differential suppression of endotoxin-inducible inflammatory cytokines by nuclear factor kappa B (NFkappaB) inhibitor in rat microglia. Nakajima, K., Matsushita, Y., Tohyama, Y., Kohsaka, S., Kurihara, T. Neurosci. Lett. (2006) [Pubmed]
  24. Induction of inhibitory factor kappaBalpha mRNA in the central nervous system after peripheral lipopolysaccharide administration: an in situ hybridization histochemistry study in the rat. Quan, N., Whiteside, M., Kim, L., Herkenham, M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  25. Oxidative stress causes nuclear factor-kappaB activation in acute hypovolemic hemorrhagic shock. Altavilla, D., Saitta, A., Guarini, S., Galeano, M., Squadrito, G., Cucinotta, D., Santamaria, L.B., Mazzeo, A.T., Campo, G.M., Ferlito, M., Minutoli, L., Bazzani, C., Bertolini, A., Caputi, A.P., Squadrito, F. Free Radic. Biol. Med. (2001) [Pubmed]
  26. Nuclear factor-kappaB as a target of cyclosporin in acute hypovolemic hemorrhagic shock. Altavilla, D., Saitta, A., Guarini, S., Galeano, M., Squadrito, G., Santamaria, L.B., Venuti, F.S., Bazzani, C., Bertolini, A., Squadrito, F. Cardiovasc. Res. (2001) [Pubmed]
  27. p38 mitogen-activated protein kinase inhibition attenuates burn-induced liver injury in rats. Chen, X.L., Xia, Z.F., Yu, Y.X., Wei, D., Wang, C.R., Ben, D.F. Burns : journal of the International Society for Burn Injuries. (2005) [Pubmed]
  28. Oscillating fluid flow inhibits TNF-alpha -induced NF-kappa B activation via an Ikappa B kinase pathway in osteoblast-like UMR106 cells. Kurokouchi, K., Jacobs, C.R., Donahue, H.J. J. Biol. Chem. (2001) [Pubmed]
  29. Double-stranded RNA signals antiviral and inflammatory programs and dysfunctional glutamate transport in TLR3-expressing astrocytes. Scumpia, P.O., Kelly, K.M., Reeves, W.H., Stevens, B.R. Glia (2005) [Pubmed]
  30. The small GTP-binding protein Rac1 induces cardiac myocyte hypertrophy through the activation of apoptosis signal-regulating kinase 1 and nuclear factor-kappa B. Higuchi, Y., Otsu, K., Nishida, K., Hirotani, S., Nakayama, H., Yamaguchi, O., Hikoso, S., Kashiwase, K., Takeda, T., Watanabe, T., Mano, T., Matsumura, Y., Ueno, H., Hori, M. J. Biol. Chem. (2003) [Pubmed]
  31. A novel antioxidant, octyl caffeate, suppression of LPS/IFN-gamma-induced inducible nitric oxide synthase gene expression in rat aortic smooth muscle cells. Hsiao, G., Shen, M.Y., Chang, W.C., Cheng, Y.W., Pan, S.L., Kuo, Y.H., Chen, T.F., Sheu, J.R. Biochem. Pharmacol. (2003) [Pubmed]
  32. Reversal Effect of Thalidomide on Established Hepatic Cirrhosis in Rats via Inhibition of Nuclear Factor-kappaB/Inhibitor of Nuclear Factor-kappaB Pathway. Lv, P., Luo, H.S., Zhou, X.P., Xiao, Y.J., Paul, S.C., Si, X.M., Zhou, Y.H. Arch. Med. Res. (2007) [Pubmed]
  33. Nitric oxide suppresses inducible nitric oxide synthase expression by inhibiting post-translational modification of IkappaB. Chang, K., Lee, S.J., Cheong, I., Billiar, T.R., Chung, H.T., Han, J.A., Kwon, Y.G., Ha, K.S., Kim, Y.M. Exp. Mol. Med. (2004) [Pubmed]
  34. Angiotensin II stimulates intercellular adhesion molecule-1 via an AT1 receptor/nuclear factor-kappaB pathway in brain microvascular endothelial cells. Liu, H.Q., Wei, X.B., Sun, R., Cai, Y.W., Lou, H.Y., Wang, J.W., Chen, A.F., Zhang, X.M. Life Sci. (2006) [Pubmed]
  35. Evidence for a role of nuclear factor-kappaB in acute hypovolemic hemorrhagic shock. Altavilla, D., Saitta, A., Squadrito, G., Galeano, M., Venuti, S.F., Guarini, S., Bazzani, C., Bertolini, A., Caputi, A.P., Squadrito, F. Surgery (2002) [Pubmed]
  36. Assessment of skin irritation and molecular responses in rat skin exposed to nonane, dodecane and tetradecane. Babu, R.J., Chatterjee, A., Singh, M. Toxicol. Lett. (2004) [Pubmed]
  37. Induction of IkappaBalpha mRNA expression in the brain by glucocorticoids: a negative feedback mechanism for immune-to-brain signaling. Quan, N., He, L., Lai, W., Shen, T., Herkenham, M. J. Neurosci. (2000) [Pubmed]
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