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Reduced gap junctional communication among astrocytes in experimental diabetes: contributions of altered connexin protein levels and oxidative-nitrosative modifications.

Authors: Ball, KK  Harik, L  Gandhi, GK  Cruz, NF  Dienel, GA 
Citation: Ball KK, etal., J Neurosci Res. 2011 Dec;89(12):2052-67. doi: 10.1002/jnr.22663. Epub 2011 May 2.
Pubmed: (View Article at PubMed) PMID:21567444
DOI: Full-text: DOI:10.1002/jnr.22663

Experimental diabetes increases production of reactive oxygen-nitrogen species and inhibits astrocytic gap junctional communication in tissue culture and brain slices from streptozotocin (STZ)-diabetic rats by unidentified mechanisms. Relative connexin (Cx) protein levels were assessed by Western blotting using extracts from cultured astrocytes grown in high (25 mmol/liter) or low (5.5 mmol/liter) glucose for 2-3 weeks and STZ-diabetic rat brain. Chemiluminescent signals for diabetic samples were normalized to those of controls on the same blot and same protein load. Growth in high glucose did not alter relative Cx26 level, whereas Cx30 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were reduced by approximately 30%, and Cx43 increased approximately 1.9-fold. In the inferior colliculus of STZ-diabetic rats, Cx30 and Cx43 levels in three of four rats were half those of controls, whereas GAPDH and actin were unaffected. Diabetes did not affect levels of Cx30, Cx43, or GAPDH in cerebral cortex, but actin level rose 24%. Cx43 was predominantly phosphorylated in control and diabetic samples, so the reduced dye transfer is not due to overall dephosphorylation of Cx43. Astrocytic growth in high glucose reduced the dye-labeled area by 75%, but 10 min of treatment with dithiothreitol restored normal dye transfer. In contrast, nitric oxide donors inhibited dye transfer among astrocytes grown in low glucose by 50-65% within 1 hr. Thus, modifications arising from oxidative-nitrosative stress, not altered connexin levels, may underlie the reduced dye transfer among severely hyperglycemic cultured astrocytes, whereas both oxidative-nitrosative stress and regionally selective down-regulation of connexin protein content may affect gap junctional communication in the brains of STZ-diabetic rats.


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RGD ID: 7364783
Created: 2013-09-27
Species: All species
Last Modified: 2013-09-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.