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Gene Review

SRL  -  sarcalumenin

Homo sapiens

Synonyms: Sarcalumenin
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Disease relevance of SRL

  • Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease [1].
  • CONCLUSION: SRL 172 was associated with an improvement in the severity of the dermatitis in children with moderate-to-severe disease [1].
  • Except for an increased incidence of pneumonia among patients receiving full-dose CsA and 3 mg/m2/day SRL, the incidences of opportunistic infections were similar in all treatment groups [2].
  • Adverse effects attributable to CsA, including hypertension and new-onset diabetes mellitus, were not exacerbated by SRL [2].
  • PURPOSE: This phase I-II study was designed to assess safety and clinical efficacy of SRL 172 vaccine in patients with advanced stage IV (AJCC) malignant melanoma [3].

High impact information on SRL

  • We propose that this lumenal Ca2+ binding glycoprotein of the sarcoplasmic reticulum be designated "sarcalumenin."[4]
  • Patients were randomly treated with corticosteroids (CS); low-dose cyclosporine (CsA) and sirolimus (SRL; group 1; n = 42); or CS, full-dose CsA, and mycophenolate mofetil (group 2; n = 48) [5].
  • All of these proteins, calsequestrin, RyR, triadin, SERCAs, and sarcalumenin, are involved in calcium uptake, storage, and release [6].
  • Specific lung resistance (SRL) was measured to assess bronchial responses to PAF, and airway responsiveness was determined by deriving a provocative dose of carbachol in breath units causing an increase in SRL to 4 L times centimeters of H2O per liters per second (PD4) from carbachol dose-response curves [7].
  • Group I (152) was given sirolimus, mycophenolate mofetil, and prednisone (SRL/MMF/P) between March 2000 and September 2002; group II (168) was given cyclosporine A (CsA)/MMF/P between January 1999 and July 2002; and group III (193) was given azathioprine (AzA)/CsA/P between January 1993 and December 1997 [8].

Chemical compound and disease context of SRL


Biological context of SRL

  • CONCLUSIONS: During a 10-year period marked by changing recipient demographics, the introduction of MMF and SRL did not result in a significant increase in transplant wound-healing complications [8].
  • Therefore, we inferred that the oral bioavailability of SRL was low [10].
  • SRL trough levels correlated with AUC (r(2) = 0.84, p < 0.001) [11].
  • In 11 unsedated sheep, specific lung resistance (SRL) was measured before, immediately after, and serially up to 8 h after inhalation challenge with A. suum antigen [12].
  • We postulated that conversion to SRL in renal recipients with KS favored regression of KS lesions without increasing the risk of graft rejection [13].

Anatomical context of SRL

  • SRL in lizards can be divided into a dorsomedial portion, which projects ipsilaterally to the spinal cord, and a ventrolateral portion which projects contralaterally [14].
  • Possible improved survival of patients with stage IV AJCC melanoma receiving SRL 172 immunotherapy: correlation with induction of increased levels of intracellular interleukin-2 in peripheral blood lymphocytes [3].
  • These results show that urate oxidase is important into peroxisomes via a common pathway with acyl-CoA oxidase, and that the C-terminal SRL sequence functions as a peroxisomal-targeting signal [15].
  • One external fixation system which has shown particularly good results is a monolateral cross-ankle articulated fixator (Orthofix SRL., Verona, Italy) which allows motion at the ankle joint as the plafond fracture is healing (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS)[16]
  • Salt-depleted rats treated with SRL (0.4-6.4 mg/kg) and/or CsA (2.5-20 mg/kg) were examined for glomerular filtration rates (GFR), lipid levels, and bone marrow cellularity [9].

Associations of SRL with chemical compounds

  • The mean values of daily steroid dose and the immunosuppressive drug C0 values were above the putative therapeutic targets: namely, CsA C0=294.9+/-153.2 ng/ml versus 150+/-50 ng/ml and SRL C0=20.1+/-14.0 ng/ml versus 10+/-5 ng/ml, respectively [17].
  • With substitution of a lysine residue for arginine in the SRL tripeptide at the C-terminus the import activity was retained [15].
  • Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy [18].
  • Four immunosuppressive regimens were evaluated as potential risk factors of TMA: cyclosporin + mycophenolate mofetil (CsA + MMF), cyclosporin + sirolimus (CsA + SRL), tacrolimus + myophenolate mofetil (FK + MMF), and tacrolimus + sirolimus (FK + SRL) [19].
  • Neither intravenously administered nor aerosolized gallopamil had a significant effect on baseline SRL [12].

Physical interactions of SRL

  • The SRL/FKBP complex binds to the protein kinase mTOR [20].

Other interactions of SRL

  • SRL 172 increases IL-2 production and the number of NK cells in vivo [21].
  • METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study [18].
  • Forty-two rugby league players, comprising 21 national league (NRL) and 21 state league (SRL) players, who regularly performed both exercises in their training, served as subjects in this investigation [22].
  • RESULTS: Morphonuclear parameters IOD, SURF, LRL, SRL and C were found to correlate with the risk of recurrence and progression of superficial bladder tumours (results for ANOVA respectively IOD P < 0.001; SURF P = 0.02; LRL P = 0.05; RLD P = 0.04; SRL P = 0.04; C P < 0.001) [23].
  • Genomic sequences encoding similar proteins containing both the sarcalumenin-like and eps15 homology domains have been identified in humans and Drosophila [24].

Analytical, diagnostic and therapeutic context of SRL

  • METHODS: Forty-one children aged 5 to 18 years with moderate-to-severe atopic dermatitis were enrolled in a randomized, double-blind, placebo-controlled trial, where they were given either one intradermal injection of killed Mycobacterium vaccae (SRL 172) or buffer solution (placebo) [1].
  • SRL may be used to reduce the exposure of renal allograft recipients to the nephrotoxic effects of CsA [25].
  • This method for therapeutic drug monitoring of SRL permits one full-time technician to analyze 100 clinical specimens per week with a 24-h turnaround time [26].
  • CONCLUSION: This initial experience suggests that a time-limited and reversible de novo HUS syndrome may be less frequent and milder among renal transplant recipients treated with SRL-based immunosuppression [17].
  • RESULTS: The incidence of biopsy-proven acute rejection episodes within the first 6 months after transplant was reduced from 32.0% in the control group to 8.5% in patients receiving SRL (1 or 3 mg/m2/day) and full-dose Sandimmune CsA (P=0.018) [2].


  1. Intradermal administration of a killed Mycobacterium vaccae suspension (SRL 172) is associated with improvement in atopic dermatitis in children with moderate-to-severe disease. Arkwright, P.D., David, T.J. J. Allergy Clin. Immunol. (2001) [Pubmed]
  2. Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group. Kahan, B.D., Julian, B.A., Pescovitz, M.D., Vanrenterghem, Y., Neylan, J. Transplantation (1999) [Pubmed]
  3. Possible improved survival of patients with stage IV AJCC melanoma receiving SRL 172 immunotherapy: correlation with induction of increased levels of intracellular interleukin-2 in peripheral blood lymphocytes. Maraveyas, A., Baban, B., Kennard, D., Rook, G.A., Westby, M., Grange, J.M., Lydyard, P., Stanford, J.L., Jones, M., Selby, P., Dalgleish, A.G. Ann. Oncol. (1999) [Pubmed]
  4. Molecular cloning and expression of cDNA encoding a lumenal calcium binding glycoprotein from sarcoplasmic reticulum. Leberer, E., Charuk, J.H., Green, N.M., MacLennan, D.H. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  5. Addition of sirolimus to cyclosporine delays the recovery from delayed graft function but does not affect 1-year graft function. Stallone, G., Di Paolo, S., Schena, A., Infante, B., Battaglia, M., Ditonno, P., Gesualdo, L., Grandaliano, G., Schena, F.P. J. Am. Soc. Nephrol. (2004) [Pubmed]
  6. The origin of tubular aggregates in human myopathies. Chevessier, F., Bauché-Godard, S., Leroy, J.P., Koenig, J., Paturneau-Jouas, M., Eymard, B., Hantaï, D., Verdière-Sahuqué, M. J. Pathol. (2005) [Pubmed]
  7. PAF-induced airway responses in sheep: effects of a PAF antagonist and nedocromil sodium. Soler, M., Mansour, E., Fernandez, A., D'Brot, J., Ahmed, T., Abraham, W.M. J. Allergy Clin. Immunol. (1990) [Pubmed]
  8. The impact of sirolimus, mycophenolate mofetil, cyclosporine, azathioprine, and steroids on wound healing in 513 kidney-transplant recipients. Flechner, S.M., Zhou, L., Derweesh, I., Mastroianni, B., Savas, K., Goldfarb, D., Modlin, C.S., Krishnamurthi, V., Novick, A. Transplantation (2003) [Pubmed]
  9. Preclinical results of sirolimus treatment in transplant models. Stepkowski, S.M. Transplant. Proc. (2003) [Pubmed]
  10. Distribution of sirolimus in rat tissue. Napoli, K.L., Wang, M.E., Stepkowski, S.M., Kahan, B.D. Clin. Biochem. (1997) [Pubmed]
  11. Short sirolimus half-life in pediatric renal transplant recipients on a calcineurin inhibitor-free protocol. Schachter, A.D., Meyers, K.E., Spaneas, L.D., Palmer, J.A., Salmanullah, M., Baluarte, J., Brayman, K.L., Harmon, W.E. Pediatric transplantation. (2004) [Pubmed]
  12. Effect of calcium antagonist gallopamil on antigen-induced early and late bronchoconstrictor responses in allergic sheep. D'Brot, J., Abraham, W.M., Ahmed, T. Am. Rev. Respir. Dis. (1989) [Pubmed]
  13. Efficacy of conversion to sirolimus in posttransplantation Kaposi's sarcoma. Gutiérrez-Dalmau, A., Sánchez-Fructuoso, A., Sanz-Guajardo, A., Mazuecos, A., Franco, A., Rial, M.C., Iranzo, P., Torregrosa, J.V., Oppenheimer, F., Campistol, J.M. Transplant. Proc. (2005) [Pubmed]
  14. The sources of supraspinal afferents to the spinal cord in a variety of limbed reptiles. I. Reticulospinal systems. Newman, D.B., Cruce, W.L., Bruce, L.L. J. Comp. Neurol. (1983) [Pubmed]
  15. Urate oxidase is imported into peroxisomes recognizing the C-terminal SKL motif of proteins. Miura, S., Oda, T., Funai, T., Ito, M., Okada, Y., Ichiyama, A. Eur. J. Biochem. (1994) [Pubmed]
  16. An articulated ankle external fixation system that can be aligned with the ankle axis. Fitzpatrick, D.C., Foels, W.S., Pedersen, D.R., Marsh, J.L., Saltzman, C.L., Brown, T.D. The Iowa orthopaedic journal. (1995) [Pubmed]
  17. De novo hemolytic uremic syndrome after kidney transplantation in patients treated with cyclosporine-sirolimus combination. Langer, R.M., Van Buren, C.T., Katz, S.M., Kahan, B.D. Transplantation (2002) [Pubmed]
  18. Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience. Zhou, J., Fan, J., Wang, Z., Wu, Z.Q., Qiu, S.J., Huang, X.W., Yu, Y., Sun, J., Xiao, Y.S., He, Y.F., Wang, Y.Q., Tang, Z.Y. World J. Gastroenterol. (2006) [Pubmed]
  19. Increased risk of thrombotic microangiopathy in patients receiving a cyclosporin-sirolimus combination. Fortin, M.C., Raymond, M.A., Madore, F., Fugère, J.A., Pâquet, M., St-Louis, G., Hébert, M.J. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. (2004) [Pubmed]
  20. Sirolimus: its role in nephrology. Lee, V.W., Chapman, J.R. Nephrology (Carlton, Vic.) (2005) [Pubmed]
  21. SRL172 (killed Mycobacterium vaccae) may augment the efficacy of trastuzumab in metastatic breast cancer patients. Altundag, K., Mohamed, A.S., Altundag, O., Silay, Y.S., Gunduz, E., Demircan, K. Med. Hypotheses (2005) [Pubmed]
  22. An analysis of the ratio and relationship between upper body pressing and pulling strength. Baker, D.G., Newton, R.U. Journal of strength and conditioning research / National Strength & Conditioning Association. (2004) [Pubmed]
  23. Prognostic evaluation of morphonuclear parameters in superficial and invasive bladder cancer. Colombel, M., De Launoit, Y., Bellot, J., Kiss, R., Abbou, C., Chopin, D. British journal of urology. (1995) [Pubmed]
  24. Expression and characterisation of a Plasmodium falciparum protein containing domains homologous to sarcalumenin and a tyrosine kinase substrate, eps15. McDaniel, J.P., Syin, C., Lin, D.T., Joshi, M.B., Li, S., Goldman, N.D. Int. J. Parasitol. (1999) [Pubmed]
  25. Improved renal function in sirolimus-treated renal transplant patients after early cyclosporine elimination. Gonwa, T.A., Hricik, D.E., Brinker, K., Grinyo, J.M., Schena, F.P. Transplantation (2002) [Pubmed]
  26. Routine clinical monitoring of sirolimus (rapamycin) whole-blood concentrations by HPLC with ultraviolet detection. Napoli, K.L., Kahan, B.D. Clin. Chem. (1996) [Pubmed]
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