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Hypophosphorylation of NF-H and NF-M subunits of neurofilaments and the associated decrease in KSPXK kinase activity in the sciatic nerves of swiss white mice inoculated in the foot pad with mycobacterium leprae.
Lepr Rev. 2009 Dec; 80(4):388-401.LR

Abstract

OBJECTIVE

To study the phosphorylation state of neurofilament (NF) proteins and activity of KSPXK kinase in the sciatic nerves of Swiss white (S/W) mice inoculated in the hind foot pads with M. leprae.

DESIGN

Test group includes S/W mice inoculated in the foot pads with freshly harvested human derived (viable) M. leprae. Control groups were constituted by (1) Age matched un-inoculated mice, (2) Mice similarly inoculated with M. smegmatis and (3) heat killed M. leprae. Phosphorylation state of NF was studied using Western blot analysis and phosphor-specific NF antibody (SMI 31; Sternberger Monoclonals, Inc.). The KSPXK kinase activity was assayed by using KSPXK fusion protein in a radiometric method using gamma(22)P ATP.

RESULTS

Several fold increase in M. leprae numbers was seen in viable M. leprae group while M. smegmatis failed to show any fold increase in the foot pads of S/W mice. Western immunoblot analysis of cytoskeletal preparation from sciatic nerves of uninoculated mice and mice inoculated with M. smegmatis showed immunoreactivity to SMI 31 antibody and protein bands corresponding to both NF-H and NF-M at all the time points from 4-20 months post inoculation. In case of viable M. leprae; SMI 31 reactive protein bands were seen at 4 months but not at any of the later intervals, i.e., between 6-20 months. With heat killed M. leprae transient loss of immunoreactivity to SMI 31 was seen. Decrease in KSPXK kinase activity was recorded in sets inoculated with viable and heat killed M. leprae, and corroborated with loss of immunoreactivity seen in WBs reacted with SMI 31 antibody.

CONCLUSIONS

Alterations in the sciatic nerve NF cytoskeleton was seen following inoculation in the hind foot pad with both viable and heat killed M. leprae. The hypophosphorylation of NF observed in this study corroborates with the earlier observations in human leprous nerves.

Authors+Show Affiliations

The Foundation for Medical Research, 84/A, R.G. Thadani Marg, Worli, Mumbai 400 018, India. fmr@fmrindia.orgNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20306637

Citation

Save, Mrudula Prakash, et al. "Hypophosphorylation of NF-H and NF-M Subunits of Neurofilaments and the Associated Decrease in KSPXK Kinase Activity in the Sciatic Nerves of Swiss White Mice Inoculated in the Foot Pad With Mycobacterium Leprae." Leprosy Review, vol. 80, no. 4, 2009, pp. 388-401.
Save MP, Shetty VP, Shetty KT. Hypophosphorylation of NF-H and NF-M subunits of neurofilaments and the associated decrease in KSPXK kinase activity in the sciatic nerves of swiss white mice inoculated in the foot pad with mycobacterium leprae. Lepr Rev. 2009;80(4):388-401.
Save, M. P., Shetty, V. P., & Shetty, K. T. (2009). Hypophosphorylation of NF-H and NF-M subunits of neurofilaments and the associated decrease in KSPXK kinase activity in the sciatic nerves of swiss white mice inoculated in the foot pad with mycobacterium leprae. Leprosy Review, 80(4), 388-401.
Save MP, Shetty VP, Shetty KT. Hypophosphorylation of NF-H and NF-M Subunits of Neurofilaments and the Associated Decrease in KSPXK Kinase Activity in the Sciatic Nerves of Swiss White Mice Inoculated in the Foot Pad With Mycobacterium Leprae. Lepr Rev. 2009;80(4):388-401. PubMed PMID: 20306637.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypophosphorylation of NF-H and NF-M subunits of neurofilaments and the associated decrease in KSPXK kinase activity in the sciatic nerves of swiss white mice inoculated in the foot pad with mycobacterium leprae. AU - Save,Mrudula Prakash, AU - Shetty,Vanaja Prabhakar, AU - Shetty,Kurudunje Taranth, PY - 2010/3/24/entrez PY - 2010/3/24/pubmed PY - 2010/4/7/medline SP - 388 EP - 401 JF - Leprosy review JO - Lepr Rev VL - 80 IS - 4 N2 - OBJECTIVE: To study the phosphorylation state of neurofilament (NF) proteins and activity of KSPXK kinase in the sciatic nerves of Swiss white (S/W) mice inoculated in the hind foot pads with M. leprae. DESIGN: Test group includes S/W mice inoculated in the foot pads with freshly harvested human derived (viable) M. leprae. Control groups were constituted by (1) Age matched un-inoculated mice, (2) Mice similarly inoculated with M. smegmatis and (3) heat killed M. leprae. Phosphorylation state of NF was studied using Western blot analysis and phosphor-specific NF antibody (SMI 31; Sternberger Monoclonals, Inc.). The KSPXK kinase activity was assayed by using KSPXK fusion protein in a radiometric method using gamma(22)P ATP. RESULTS: Several fold increase in M. leprae numbers was seen in viable M. leprae group while M. smegmatis failed to show any fold increase in the foot pads of S/W mice. Western immunoblot analysis of cytoskeletal preparation from sciatic nerves of uninoculated mice and mice inoculated with M. smegmatis showed immunoreactivity to SMI 31 antibody and protein bands corresponding to both NF-H and NF-M at all the time points from 4-20 months post inoculation. In case of viable M. leprae; SMI 31 reactive protein bands were seen at 4 months but not at any of the later intervals, i.e., between 6-20 months. With heat killed M. leprae transient loss of immunoreactivity to SMI 31 was seen. Decrease in KSPXK kinase activity was recorded in sets inoculated with viable and heat killed M. leprae, and corroborated with loss of immunoreactivity seen in WBs reacted with SMI 31 antibody. CONCLUSIONS: Alterations in the sciatic nerve NF cytoskeleton was seen following inoculation in the hind foot pad with both viable and heat killed M. leprae. The hypophosphorylation of NF observed in this study corroborates with the earlier observations in human leprous nerves. SN - 0305-7518 UR - https://www.unboundmedicine.com/medline/citation/20306637/Hypophosphorylation_of_NF_H_and_NF_M_subunits_of_neurofilaments_and_the_associated_decrease_in_KSPXK_kinase_activity_in_the_sciatic_nerves_of_swiss_white_mice_inoculated_in_the_foot_pad_with_mycobacterium_leprae_ L2 - https://medlineplus.gov/mycobacterialinfections.html DB - PRIME DP - Unbound Medicine ER -