12/15-Lipoxygenase inhibition counteracts MAPK phosphorylation in mouse and cell culture models of diabetic peripheral neuropathy

Roman Stavniichuk; Alexander A. Obrosov; Viktor R. Drel; Jerry L. Nadler; Irina G. Obrosova; Mark A. Yorek

doi:10.4236/jdm.2013.33015

Back

12/15-Lipoxygenase inhibition counteracts MAPK phosphorylation in mouse and cell culture models of diabetic peripheral neuropathy

Journal article

Open access

12/15-Lipoxygenase inhibition counteracts MAPK phosphorylation in mouse and cell culture models of diabetic peripheral neuropathy

Roman Stavniichuk, Alexander A. Obrosov, Viktor R. Drel, Jerry L. Nadler, Irina G. Obrosova and Mark A. Yorek

Journal of diabetes mellitus, Vol.3(3), pp.101-110

08/01/2013

DOI: 10.4236/jdm.2013.33015

PMCID: PMC3808974

PMID: 24175152

Files and links (1)

url

https://doi.org/10.4236/jdm.2013.33015View

Published (Version of record) Open Access

Abstract

Background: Increased mitogen-activated protein kinase (MAPK) phosphorylation has been detected in peripheral nerve of human subjects and animal models with diabetes as well as high-glucose exposed human Schwann cells, and have been implicated in diabetic peripheral neuropathy. In our recent studies, leukocytetype 12/15-lipoxygenase inhibition or gene deficiency alleviated large and small nerve fiber dysfunction, but not intraepidermal nerve fiber loss in streptozotocin-diabetic mice. Methods: To address a mechanism we evaluated the potential for pharmacological 12/15-lipoxygenase inhibition to counteract excessive MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy. C57Bl6/J mice were made diabetic with streptozotocin and maintained with or without the 12/15-lipoxygenase inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC). Human Schwann cells were cultured in5.5 mMor30 mMglucose with or without CDC. Results: 12(S) HETE concentrations (ELISA), as well as 12/15-lipoxygenase expression and p38 MAPK, ERK, and SAPK/JNK phosphorylation (all by Western blot analysis) were increased in the peripheral nerve and spinal cord of diabetic mice as well as in high glucose-exposed human Schwann cells. CDC counteracted diabetes-induced increase in 12(S)HETE concentrations (a measure of 12/15-lipoxygenase activity), but not 12/15-lipoxygenase overexpression, in sciatic nerve and spinal cord. The inhibitor blunted excessive p38 MAPK and ERK, but not SAPK/ JNK, phosphorylation in sciatic nerve and high glucose exposed human Schwann cells, but did not affect MAPK, ERK, and SAPK/JNK phosphorylation in spinal cord. Conclusion: 12/15-lipoxygenase inhibition counteracts diabetes related MAPK phosphorylation in mouse and cell culture models of diabetic neuropathy and implies that 12/15-lipoxygenase inhibitors may be an effective treatment for diabetic peripheral neuropathy.

Diabetes

Lipoxygenase

Mitogen-Activated Protein Kinase

Neuropathy

Schwann Cells

Details

Title: Subtitle: 12/15-Lipoxygenase inhibition counteracts MAPK phosphorylation in mouse and cell culture models of diabetic peripheral neuropathy
Creators: Roman Stavniichuk - Pennington Biomedical Research Center
Alexander A. Obrosov - University of Iowa
Viktor R. Drel - University of Iowa
Jerry L. Nadler - University of Iowa
Irina G. Obrosova - Louisiana State University
Mark A. Yorek - University of Iowa
Resource Type: Journal article
Publication Details: Journal of diabetes mellitus, Vol.3(3), pp.101-110
DOI: 10.4236/jdm.2013.33015
PMID: 24175152
PMCID: PMC3808974
NLM abbreviation: J Diabetes Mellitus
ISSN: 2160-5831
eISSN: 2160-5858
Grant note: R01 DK077141 || DK / National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
Language: English
Date published: 08/01/2013
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984363432702771

Metrics

11 Record Views