Skip to main content

Advertisement

SpringerLink
Log in

Spleen-specific isoforms of Pax5 and Ataxin-7 as potential proteomic markers of lymphoma-affected spleen

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The splenomegaly, enlargement of spleen, has been observed in several diseases. It has been intended to evaluate histochemical alterations, spleen-specific enzymatic and proteomic markers during splenomegaly, and lympho-proliferative disorders from spleen of mice bearing Dalton’s lymphoma. The higher expression of c-fos, c-jun, and MAPK testifies proliferation of lymphocytes. The lower expression of Pax5, higher expression of CD3, and the presence of additional form of Zap-70 suggest hypertrophy of follicles and splenomegaly influenced by weak B-cell receptor-mediated signaling, but activated T-cell receptor-mediated signaling. Simultaneously, lower levels of SOD, NDR2, and MIB2 and higher expression levels of Ataxin-7 and LDH also suggest impact of stress either as a cause or effect of cell proliferation. Spleen-specific isoform of Pax5, NDR2, MIB2, and Ataxin-7 can be considered as spleen-specific unique molecular markers for the evaluation of splenomegaly and lympho-proliferative disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Kaplan B, Jie T, Diana R, Renz J, Whinery A, Stubbs N, Bracamonte E, Spier C, Schubart P, Rilo H, Gruessner R (2010) Histopathology and immunophenotype of the spleen during acute antibody-mediated rejection. Am J Transpl 10:1316–1320

    Article  CAS  Google Scholar 

  2. Shanker A, Singh SM (2003) Immunopotentiation in mice bearing a spontaneous transplantable T-cell lymphoma: role of thymic extract. Neoplasma 50:272–279

    CAS  PubMed  Google Scholar 

  3. Yang JC, Rickman LS, Bosser SK (1991) The clinical diagnosis of splenomegaly. West J Med 155:47–52

    PubMed Central  CAS  PubMed  Google Scholar 

  4. Gardenghi S, Ramos P, Marongiu MF, Melchiori L, Breda L, Guy E, Muirhead K, Rao N, Roy CN, Andrews NC, Nemeth E, Follenzi A, An X, Mohandas N, Ginzburg Y, Rachmilewitz EA, Giardina PJ, Grady RW, Rivella S (2010) Hepcidin as a therapeutic tool to limit iron overload and improve anemia in β-thalassemic mice. J Clin Invest 120:4466–4477

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Wandroo F, Bell A, Darbyshire P, Pratt G, Stankovic T, Gordon J, Lawson S, Moss P (2008) ZAP-70 is highly expresses in most cases of childhood pre-B cell acute lymphoblastic leukemia. Int J Lab Hematol 30:149–157

    Article  CAS  PubMed  Google Scholar 

  6. Butrym A, Prochorec-Sobieszek M, Dzietczenia J, Mazur G (2014) Unclassified small B-cell lymphoma with marked plasmacytic differentiation and Mott cell formation. Leuk & Lymphoma 55:1681–1683

    Article  Google Scholar 

  7. Matthias P, Rolink AG (2005) Transcriptional networks in developing and mature B cells. Nat Rev Immunol 5:497–508

    Article  CAS  PubMed  Google Scholar 

  8. Chen L, Huynth L, Apgar J, TangL, Rassenti L, Weiss A (2008) Zap-70 enhance IgM signaling independent of its kinase activity in chronic lymphocytic leukemia. Blood 111:2685–2692

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Bharti B, Mishra R (2011) Isoforms of Pax5 and co-regulation of T- and B-cells associated genes influence phenotypic traits of ascetic cells causing Dalton’s lymphoma. Biochim Biophys Acta- MCR 1813:2071–2078

    Article  CAS  Google Scholar 

  10. Laemmli UK (1970) Cleavage of structural proteins during assembly of head of bacteriophage-T4. Nature 227:680

    Article  CAS  PubMed  Google Scholar 

  11. Shevchenko A, Tomas H, Havlis J, Olsen JV, Mann M (2006) In-gel digestion for mass spectrophotometric characterization of proteins and proteomes. Nat Protoc 6:2856–2860

    Google Scholar 

  12. Elmore SA (2006) Enhanced histopathology of the spleen. Toxicol Pathol 34:648–655

    Article  PubMed Central  PubMed  Google Scholar 

  13. Christensen BE, Jonsson V, Videbaek A (1983) The spleen in lymphoproliferative disorders. Clin Haematol 12:517–533

    CAS  PubMed  Google Scholar 

  14. Smith L, Luna G, Merg AR, McNevin MS, Moore MR, Bax TW (2004) Laparoscopic splenectomy for treatment of splenomegaly. Am J Surg 187:618–620

    Article  PubMed  Google Scholar 

  15. Chu HB, Zhang TG, Zhao JH, Jian FG, Xu YB, Wang T, Wang M, Tang JY, Sun HJ, Guo WJ, Zhu XJ (2014) Assessment of immune cells and function of the residual spleen after subtotal splenectomy due to splenomegaly in cirrhosis patients. BMC Immunol 15:42–49

    Article  PubMed Central  PubMed  Google Scholar 

  16. Jensen KC, Higgins JPT, Montgomery K, Kaygusuz G, Rijn MVD, Natkunam Y (2007) The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms. Mod Pathol 20:871–877

    Article  CAS  PubMed  Google Scholar 

  17. Lowen M, Scott G, Zwollo P (2001) Functional analyses of two alternative isoforms of the transcription factor Pax-5. J Biol Chem 276:42565–42574

    Article  CAS  PubMed  Google Scholar 

  18. Dorfler P, Busslinger M (1996) C-terminal activating and inhibitory domains determine the transactivation potential of BSAP (Pax-5), Pax-2 and Pax-8. EMBO J 15:1971–1982

    PubMed Central  CAS  PubMed  Google Scholar 

  19. Kimura M, Yamaguchi M, Nakamura S, Imai H, Ueno S, Ogawa S, Miyazaki K, Oka K, Ohno T, Kita K, Kobayashi T, Shiku H (2007) Clinicopathologic significance of loss of CD19 expression in diffuse large B-cell lymphoma. Int J Hematol 85:41–48

    Article  CAS  PubMed  Google Scholar 

  20. Engel P, Zhou LJ, Ord DC, Sato S, Koller B, Tedder TF (1995) Abnormal B lymphocyte development, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule. Immunity 3:39–50

    Article  CAS  PubMed  Google Scholar 

  21. Lin J, Weiss A (2001) Identification of minimal tyrosine residues required for linker for activation of T cell function. J Biol Chem 276:29588–29595

    Article  CAS  PubMed  Google Scholar 

  22. Okkenhaug K, Bilancio A, Emery JL, Vanhaesebroek B (2004) Phosphoinositide 3-kinase in T cell activation and survival. Biochem Soc Trans 32:332–335

    Article  CAS  PubMed  Google Scholar 

  23. Levin AJ (1997) P53, the cellular gatekeeper for growth and division. Cell 88:323–331

    Article  Google Scholar 

  24. Stuart ET, Haffner R, Oren M, Gruss P (1995) Loss of p53 function through PAX-mediated transcriptional repression. EMBO J 14:5638–5645

    PubMed Central  CAS  PubMed  Google Scholar 

  25. Babjuk M, Soukup V, Mares J, Duskova J, Sedlacek Z, Trkova M, Pecen L, Dvoracek J, Hanus T, Kocvara R, Novak J, Povysil C (2002) The expression of PAX5, p53 immunohistochemistry and p53 mutation analysis in superficial bladder carcinoma tissue: correlation with pathological findings and clinical outcome. Int Urol Nephrol 34:495–501

    Article  CAS  PubMed  Google Scholar 

  26. Babjuk M, Soukup V, Mares J, Duskova J, Pecen L, Pesl M, Pavlik I, DvorRcek J (2006) Association of PAX5 expression with clinical outcome in patients with TaT1 transitional cell carcinoma of the bladder. Urology 67:756–761

    Article  CAS  PubMed  Google Scholar 

  27. Proulx M, Cayer MP, Drouin M, Laroche A, Jung D (2010) Overexpression of PAX5 induces apoptosis in multiple myeloma cells. Int J Hematol 92:451–462

    Article  CAS  PubMed  Google Scholar 

  28. Davidson D, Bakinowski M, Thomas ML, Horejsi V, Veillette A (2003) Phosphorylation dependent regulation of T-cell activation by PAG/Cbp, a lipid raft-associated transmembrane adaptor. Mol Cell Biol 23:2017–2028

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Dalton TP, Shertzer HG, Puga A (1999) Regulation of gene expression by reactive oxygen. Annu Rev Pharmacol Toxicol 39:67–101

    Article  CAS  PubMed  Google Scholar 

  30. Brecht K, Simonen M, Brachat A, Heim J (2005) Upregulation of alpha globin promotes apoptotic cell death in the hematopoietic cell line FL5.12. Apoptosis 10:1043–1062

    Article  CAS  PubMed  Google Scholar 

  31. Vichalkovski A, Gresko E, Cornils H, Hergovich A, Schmitz D, Hemmings BA (2005) NDR kinase is activated by RASSF1A/MST1 in response to Fas receptor stimulation and promotes apoptosis. Curr Biol 18:1889–1895

    Article  Google Scholar 

  32. Koo BK, Yoon KJ, Yoo KW, Lim HS, Song R, So JH, Kim CH, Kong YY (2005) Mind bomb 2 is an E3 ligase for Notch ligand. J Biol Chem 280:22335–22342

    Article  CAS  PubMed  Google Scholar 

  33. Huang PY, Best OG, Almazi JG, Belov L, Davis ZA, Majid A, Dyer MJ, Pascovici D, Mulligan SP, Chrisopherson RI (2014) Cell surface phenotype profiles distinguish stable and progressive chronic lympnocyticleukemia. Leuk Lymphoma 55:2085–2092

    Article  CAS  PubMed  Google Scholar 

  34. Lu R, Jiang M, Chen Z, Xu X, Hu H, Zhao X, Gao X, Guo L (2013) Lactate dehydrogenase 5 expression in non-hodgkin lymphoma is associated with the induced hypoxia regulated protein and poor prognosis. PLoS ONE 8:e74853

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Weinreb NJ, Rosenbloom BE (2013) Splenomegaly, hypersplenism, and hereditary disorder with splenomegaly. Open J genetics 3:24–43

    Article  Google Scholar 

Download references

Acknowledgments

Kind gift of anti-Pax5 from Prof. S. Nutt is gratefully acknowledged. We are thankful to Prof. Mohan Kumar and Prof. Manoj Pandey, IMS, BHU for their critical discussion and suggestions on cyto-pathological data. Authors thank Suman Mishra for her help in preparing this manuscript.

Conflict of interest

The Authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Zoology, Banaras Hindu University, Varanasi, 221005, India

    Brij Bharti & Rajnikant Mishra

Authors
  1. Brij Bharti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rajnikant Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rajnikant Mishra.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bharti, B., Mishra, R. Spleen-specific isoforms of Pax5 and Ataxin-7 as potential proteomic markers of lymphoma-affected spleen. Mol Cell Biochem 402, 181–191 (2015). https://doi.org/10.1007/s11010-014-2325-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-014-2325-7

Keywords

Search

Navigation