Decreases of ganglioside GM3 in streptozotocin-induced diabetic glomeruli of rats.
Ganglioside GM(3) (NeuAcalpha3Galbeta4Glcbeta1Cer) is known to regulate the proliferation of many cell types and to maintain the charge-selective filtration barrier of glomeruli. Based on these, this study examined whether altered expression of ganglioside GM(3) was pathologically related with glomerular hypertrophy and proteinuria occurring in diabetic human and rat kidneys. Diabetic rats were produced by intraperitoneal injection of streptozotocin (80 mg/kg, I.P.). At 15 days after the induction of diabetes, glomerular volume and fibrotic matrix were dramatically elevated, whereas glomerular sialic acid contents were significantly reduced compared with control. Based upon mobility on high-performance thin-layer chromatography (HPTLC) and reactivity to anti-GM(3) monoclonal antibody, normal glomeruli showed a complex ganglioside pattern that consisted of six different components of gangliosides, mainly GM(3), and diabetes caused a severe reduction of these gangliosides with apparent changes in the composition of major ganglioside GM(3). Semi-quantitative analysis by HPTLC showed that ganglioside GM(3) was reduced to 57% of control in diabetic glomeruli. A prominent immunofluorescence microscopy showed a dramatic disappearance of GM(3) expression in diabetic glomeruli. These results indicate that diabetic glomeruli can be characterized by decreases of glomerular sialic acid content and ganglioside GM(3) expression, which may cause loss of charge-selective filtration barrier in renal glomeruli. These changes may be account, at least in part, for the development of glomerular hypertrophy and proteinuria seen in the early stage of diabetic glomerulopathy.
Kwak
Dong Hoon
DH
Division of Biological Science, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea.
Rho
Young Il
YI
Kwon
Oh Deog
OD
Ahan
Seon Ho
SH
Song
Ju Hung
JH
Choo
Young Kug
YK
Kim
Sung Jo
SJ
Choi
Bong Kyu
BK
Jung
Kyu Yong
KY
D000818:Animals; D002855:Chromatography, Thin Layer; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000096:biosynthesis*; D006984:Hypertrophy; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008856:Microscopy, Fluorescence; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012794:Sialic Acids / Q000378:metabolism
D005679:G(M3) Ganglioside; D012794:Sialic Acids