High glucose-induced activation of the polyol pathway and changes of gene expression profiles in immortalized adult mouse Schwann cells IMS32.
We investigated the polyol pathway activity and the gene expression profiles in immortalized adult mouse Schwann cells (IMS32) under normal (5.6 mM) and high (30 and 56 mM) glucose conditions for 7-14 days in culture. Messenger RNA and the protein expression of aldose reductase (AR) and the intracellular sorbitol and fructose contents were up-regulated in IMS32 under high glucose conditions compared with normal glucose conditions. By employing DNA microarray and subsequent RT-PCR/northern blot analyses, we observed significant up-regulation of the mRNA expressions for serum amyloid A3 (SAA3), angiopoietin-like 4 (ANGPTL4) and ecotropic viral integration site 3 (Evi3), and the down-regulation of aldehyde reductase (AKR1A4) mRNA expression in the cells under high glucose (30 mM) conditions. The application of an AR inhibitor, SNK-860, to the high glucose medium ameliorated the increased sorbitol and fructose contents and the reduced AKR1A4 mRNA expression, while it had no effect on mRNA expressions for SAA3, ANGPTL4 or Evi3. Considering that the exposure to the high glucose (>or= 30 mM) conditions mimicking hyperglycaemia in vivo accelerated the polyol pathway in IMS32, but not in other previously reported Schwann cells, the culture system of IMS32 under those conditions may provide novel findings about the polyol pathway-related abnormalities in diabetic neuropathy.
Sango
Kazunori
K
Department of Developmental Morphology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan. kazsango@tmin.ac.jp
Suzuki
Takeshi
T
Yanagisawa
Hiroko
H
Takaku
Shizuka
S
Hirooka
Hiroko
H
Tamura
Miyuki
M
Watabe
Kazuhiko
K
D000449:Aldehyde Reductase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005632:Fructose / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D009994:Osmolar Concentration; D010525:Peripheral Nerves / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011108:Polymers / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013012:Sorbitol / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
D018076:DNA, Complementary; D011108:Polymers; D012333:RNA, Messenger; C024617:polyol; D005632:Fructose; D013012:Sorbitol; D000449:Aldehyde Reductase; D013385:Succinate Dehydrogenase; D005947:Glucose