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Gene Review

Gif  -  gastric intrinsic factor

Rattus norvegicus

Synonyms: Gastric intrinsic factor, IF, INF, Intrinsic factor
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Disease relevance of Gif

  • We studied the effect of chronic mechanical overloading on the isoenzyme composition of rat cardiac myosin in several experimental models: aortic stenosis (AS), aortic incompetence (AI), aortocaval fistula (ACF), overload of the non-infarcted area after left coronary ligation (INF), and overload of the spontaneously hypertensive rats (SHR) [1].
  • Proteinuria was also greater in the INF group at both time periods [2].
  • In a 100% fatal rat malignant glioma model, genetically modified tumors secreting INF-gamma intracerebrally generate an immune response resulting in a substantial increase in survival time, tumor rejection and specific systemic immunity [3].
  • Because of increased age-related susceptibility to sepsis, we hypothesized that hearts from old (28-29 months) adult rats would exhibit greater beta-adrenergic hyporesponsiveness than young (6-8 months) following lipopolysaccharide (LPS, 6 mg/kg) with and without interferon gamma (INF-gamma, 5000 units) [4].
  • At four weeks, there was 128% increase in right ventricular hypertrophy in the hearts from INF vs. CON [5].

High impact information on Gif

  • The purpose of this study was to determine whether all commercially available forms of interferon alfa (INF alpha) have the same inhibitory effect on hepatic regeneration and whether this inhibitory effect can be prevented by putrescine, a hepatic growth promotor [6].
  • These TCR-gamma delta+ T-cells are demonstrated to produce high levels of INF-gamma in response to OVA stimulation, and this provides a potential mechanism for the inhibition of Th2 cell proliferation, resulting in suppression of IgE production [7].
  • Intrinsic factor has two binding sites, one each for cobalamin and for the ileal receptor recognizing the intrinsic factor-cobalamin complex [8].
  • Intrinsic factor, which binds the cobalamin cofactor of leucine 2,3-aminomutase, effectively blocked the beta-keto pathway [9].
  • In summary, higher aldosterone and plasma renin levels distinguish the INF model from the POL and likely contribute to the greater proteinuria and hypertension in the INF model [2].

Biological context of Gif

  • Furthermore, there was a twofold increase in myocyte apoptosis within the RM in INF vs. CON [5].
  • There was a 52% increase in TBARS within the RM from INF vs. CON, suggesting increased lipid peroxidation [5].
  • Western blot analysis showed 3.8 fold increase in JNK phosphorylation within the RM from INF vs. CON, confirmed by a 4.2 fold increase in JNK kinase activity [5].
  • We conclude that the RM from INF is associated with activation of JNK, increased oxidative stress and enhanced myocyte apoptosis [5].
  • We also measured water intake during and after INF of the same amount of 1 M NaCl solution in conscious JR (n = 6) and AR (n = 6) [10].

Anatomical context of Gif

  • When IL-1beta, but not TNF-alpha or INF-gamma, was injected in combination with LPS, a strong COX-2-ir was associated with the perivascular cells of most blood vessels in the injected hemisphere and of several of those in the uninjected hemisphere [11].
  • In TR-INF the left and right ventricular weights, and myocyte length and width were 15, 23, 12, and 20% less than in SED-INF [12].
  • Training started 4 weeks after ligation of the left coronary artery (TR-INF, n=11) or sham operation (TR-SHAM, n=6) [12].
  • Lymphocyte adhesion was low to unstimulated microvascular EC and augmented by pretreatment of EC with INF gamma, TNF alpha and LPS [13].
  • Our data show that all INF-gamma induce DNA synthesis in rat astrocytes but only rat and mouse and not the human IFN-gamma will induce Ia expression [14].

Associations of Gif with chemical compounds

  • Primary mixed glial cultures exposed to lipopolysaccharide (LPS) or a combination of LPS and gamma-interferon (INF-gamma) produce nitrite, a breakdown product of NO formation, in a dose-dependent manner [15].
  • In mixed glial-neuronal cultures exposed to 50 ng LPS or 5 ng LPS and 1 microgram INF-gamma, neurons begin to die at 48 hr, approx. 24-36 hr after detectable nitrite production [15].
  • Additionally isoproterenol-stimulated cAMP elaboration was less in old (1950+/-160 fmol/min/g) v young (2440+/-170 fmol/min/g, P=0.05) LPS/INF-gamma hearts [4].
  • The enzymatic activities of catalase and Mn-SOD (mitochondrial) showed a significant increase after LPS/INF gamma treatment, which was abolished by NMMA [16].
  • Semi-quantitative cytokine analysis revealed that the mRNA expression of TNF-alpha and INF-gamma in spinal cords and spleens of actarit treated active EAE rats was significantly reduced compared with vehicle treated EAE rats [17].

Analytical, diagnostic and therapeutic context of Gif

  • Likewise, the NK-2, but not NK-1, antagonist decreased both Th1 (INF-gamma) and Th2 (IL-4 and -5) cytokine expression in BAL cells by in situ hybridization [18].
  • In primary astroglial cell cultures, treatment for 18 h with increasing concentrations of LPS and INF gamma, produced an increase in the amount of mitochondrial encoded CO-I and -II subunits, with no significant modifications of nuclear encoded subunit IV [16].
  • Real-time PCR was used to assess IL-18 and INF-gamma mRNA expression in tissue and cell isolates [19].
  • The Na concentrations in plasma ([Na]pl) and [Na]csf were measured during intravenous infusion of 1 M NaCl solution (INF, 0.2 ml/100 g body wt. for 10 min) and for 20 min thereafter in anesthetized rats [10].
  • Factors which regulate Intrinsic Factor (IF) content and IF mRNA level were examined with an abc-ELISA and Northern blot analysis in growing rats, and compared with pepsinogen (Pg) and in terms of the increased need for vitamin B12 (V.B12) [20].


  1. Myosin isoenzyme changes in several models of rat cardiac hypertrophy. Mercadier, J.J., Lompré, A.M., Wisnewsky, C., Samuel, J.L., Bercovici, J., Swynghedauw, B., Schwartz, K. Circ. Res. (1981) [Pubmed]
  2. The renin-aldosterone axis in two models of reduced renal mass in the rat. Ibrahim, H.N., Hostetter, T.H. J. Am. Soc. Nephrol. (1998) [Pubmed]
  3. Priming in the brain, an immunologically privileged organ, elicits anti-tumor immunity. Fathallah-Shaykh, H.M., Gao, W., Cho, M., Herrera, M.A. Int. J. Cancer (1998) [Pubmed]
  4. Augmented age-associated innate immune responses contribute to negative inotropic and lusitropic effects of lipopolysaccharide and interferon gamma. Rosas, G.O., Zieman, S.J., Donabedian, M., Vandegaer, K., Hare, J.M. J. Mol. Cell. Cardiol. (2001) [Pubmed]
  5. Activation of JNK in the remote myocardium after large myocardial infarction in rats. Li, W.G., Zaheer, A., Coppey, L., Oskarsson, H.J. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  6. The differential effects of three forms of interferon alfa on hepatic regeneration after partial hepatectomy in the rat. Wong, S., Gauthier, T., Kaita, K.D., Minuk, G.Y. Hepatology (1995) [Pubmed]
  7. Gamma delta T cells down-regulate primary IgE responses in rats to inhaled soluble protein antigens. McMenamin, C., McKersey, M., Kühnlein, P., Hünig, T., Holt, P.G. J. Immunol. (1995) [Pubmed]
  8. The intrinsic factor (IF)-cobalamin receptor binding site is located in the amino-terminal portion of IF. Tang, L.H., Chokshi, H., Hu, C.B., Gordon, M.M., Alpers, D.H. J. Biol. Chem. (1992) [Pubmed]
  9. The relative carbon flux through the alpha- and the beta-keto pathways of leucine metabolism. Poston, J.M. J. Biol. Chem. (1984) [Pubmed]
  10. Changes in Na concentration in cerebrospinal fluid during acute hypernatremia and their effect on drinking in juvenile rats. Doi, Y., Nose, H., Morimoto, T. Physiol. Behav. (1992) [Pubmed]
  11. In vivo expression of cyclooxygenase-2 in rat brain following intraparenchymal injection of bacterial endotoxin and inflammatory cytokines. Minghetti, L., Walsh, D.T., Levi, G., Perry, V.H. J. Neuropathol. Exp. Neurol. (1999) [Pubmed]
  12. Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility, Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction. Wisløff, U., Loennechen, J.P., Currie, S., Smith, G.L., Ellingsen, Ø. Cardiovasc. Res. (2002) [Pubmed]
  13. Effect of a monoclonal antibody to VLA-4 on lymphocyte adherence to microvascular and aortic endothelial cells. Wykretowicz, A., Issekutz, T.B. J. Mol. Cell. Cardiol. (1993) [Pubmed]
  14. Tetraethylammonium, a K+ channel blocker, inhibits interferon-gamma-induced major histocompatibility class II antigen (Ia) expression and DNA synthesis in rat astrocytes. Ohira, K., Vayuvegula, B., Murakami, M., Gollapudi, S., Frohman, E., van den Noort, S., Gupta, S. J. Neuroimmunol. (1991) [Pubmed]
  15. Expression of inducible nitric oxide synthase causes delayed neurotoxicity in primary mixed neuronal-glial cortical cultures. Dawson, V.L., Brahmbhatt, H.P., Mong, J.A., Dawson, T.M. Neuropharmacology (1994) [Pubmed]
  16. Effect of nitric oxide synthase induction on the expression of mitochondrial respiratory chain enzyme subunits in mixed cortical and astroglial cell cultures. Nicoletti, V.G., Caruso, A., Tendi, E.A., Privitera, A., Console, A., Calabrese, V., Spadaro, F., Ravagna, A., Copani, A., Stella, A.M. Biochimie (1998) [Pubmed]
  17. Suppressive effects of 4-acetylaminophenylacetic acid (actarit) on experimental autoimmune encephalomyelitis in rats. Kawai, K., Kobayashi, Y., Hirayama, M., Shiratori, M., Sobue, G. Immunopharmacology (1998) [Pubmed]
  18. Dichotomy between neurokinin receptor actions in modulating allergic airway responses in an animal model of helper T cell type 2 cytokine-associated inflammation. Maghni, K., Taha, R., Afif, W., Hamid, Q., Martin, J.G. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  19. Macrophage-derived interleukin-18 in experimental renal allograft rejection. Wyburn, K., Wu, H., Yin, J., Jose, M., Eris, J., Chadban, S. Nephrol. Dial. Transplant. (2005) [Pubmed]
  20. Some factors which influence intrinsic factor content and its mRNA level in the rat stomach. Tani, S., Ohtani, K., Tanaka, T. Biol. Pharm. Bull. (2000) [Pubmed]
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