|
 |
|
|||||||
|
|||||||||
DOI: 10.2337/db06-0067
© 2006 by the American Diabetes Association
Poly(ADP-Ribose) Polymerase Inhibition Alleviates Experimental Diabetic Sensory Neuropathy
1 Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana
2 Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
3 Laboratory of Physiological Studies, National Insitutes of Health/National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland
4 Veteran Affairs Medical Center and Department of Internal Medicine, University of Iowa, Iowa City, Iowa
Address correspondence and reprint requests to Irina G. Obrosova, PhD, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd., Baton Rouge, LA 70808. E-mail: obrosoig{at}pbrc.edu
Abbreviations:
DRG, dorsal root ganglia; ISO, 1,5-isoquinolinediol; PARP, poly(ADP-ribose) polymerase; STZ, streptozotocin; TUNEL, transferase-mediated dUTP nick-end labeling
Poly(ADP-ribose) polymerase (PARP) activation is emerging as a fundamental mechanism in the pathogenesis of diabetes complications including diabetic neuropathy. This study evaluated the role of PARP in diabetic sensory neuropathy. The experiments were performed in control and streptozotocin-induced diabetic rats treated with or without the PARP inhibitor 1,5-isoquinolinediol (ISO; 3 mg · kg–1 · day–1 i.p.) for 2 weeks after 2 weeks without treatment. Diabetic rats developed thermal hyperalgesia (assessed by paw-withdrawal and tail-flick tests), mechanical hyperalgesia (von Frey anesthesiometer/rigid filaments and Randall-Sellito tests), tactile allodynia (flexible von Frey filaments), and increased flinching behavior in phases 1 and 2 of the 2% formalin pain test. They also had clearly manifest increase in nitrotyrosine and poly(ADP-ribose) immunoreactivities in the sciatic nerve and increased superoxide formation (hydroxyethidine method) and nitrotyrosine immunoreactivity in vasa nervorum. ISO treatment alleviated abnormal sensory responses, including thermal and mechanical hyperalgesia and tactile allodynia as well as exaggerated formalin flinching behavior in diabetic rats, without affecting the aforementioned variables in the control group. Poly(ADP-ribose) and, to a lesser extent, nitrotyrosine abundance in sciatic nerve, as well as superoxide and nitrotyrosine formation in vasa nervorum, were markedly reduced by ISO therapy. Apoptosis in dorsal root ganglion neurons (transferase-mediated dUTP nick-end labeling assay) was not detected in any of the groups. In conclusion, PARP activation contributes to early diabetic sensory neuropathy by mechanisms that may include oxidative stress but not neuronal apoptosis.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  I. G. Obrosova, O. Ilnytska, V. V. Lyzogubov, I. A. Pavlov, N. Mashtalir, J. L. Nadler, and V. R. Drel High-Fat Diet Induced Neuropathy of Pre-Diabetes and Obesity: Effects of "Healthy" Diet and Aldose Reductase Inhibition Diabetes, October 1, 2007; 56(10): 2598 - 2608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, J. S. Beckman, and L. Liaudet Nitric Oxide and Peroxynitrite in Health and Disease Physiol Rev, January 1, 2007; 87(1): 315 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Stevens, F. Li, V. R. Drel, O. I. Abatan, H. Kim, D. Burnett, D. Larkin, and I. G. Obrosova Nicotinamide Reverses Neurological and Neurovascular Deficits in Streptozotocin Diabetic Rats J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 458 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. R. Drel, N. Mashtalir, O. Ilnytska, J. Shin, F. Li, V. V. Lyzogubov, and I. G. Obrosova The Leptin-Deficient (ob/ob) Mouse: A New Animal Model of Peripheral Neuropathy of Type 2 Diabetes and Obesity Diabetes, December 1, 2006; 55(12): 3335 - 3343. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |