Effects of alpha-lipoic acid on transforming growth factor beta1-p38 mitogen-activated protein kinase-fibronectin pathway in diabetic nephropathy.
In diabetic nephropathy, transforming growth factor beta1 (TGFbeta1) is related to p38 mitogen-activated protein kinase (MAPK) that induces production of fibronectin in mesangial cells. We investigated the effects of alpha-lipoic acid (ALA), a potent antioxidant, on proteinuria and TGFbeta1-p38 MAPK-fibronectin pathway in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After ALA treatment for 5 weeks in OLETF rats at 30 weeks of age, plasma malondialdehyde, urinary protein excretion, renal cortical TGFbeta1, and fibronectin protein levels were decreased; and urinary protein excretion was positively correlated with renal cortical TGFbeta1 and fibronectin protein levels. Phospho-form but not total-form levels as well as fold activations of each protein consisting of p38 MAPK pathway were also attenuated. These results suggest that ALA ameliorates proteinuria by attenuating expressions of TGFbeta1 and fibronectin proteins, and these favorable effects are related to inhibition of phosphorylating activation of p38 MAPK pathway in renal cortex of OLETF rats.
Department of Endocrinology and Metabolism, College of Medicine, Hallym University, ChunCheon 200-704, Republic of Korea. leesj@hallym.ac.kr
Seong Jin
SJ
Lee
Jun Goo
JG
Kang
Ohk Hyun
OH
Ryu
Chul Sik
CS
Kim
Sung-Hee
SH
Ihm
Moon Gi
MG
Choi
Hyung Joon
HJ
Yoo
Dong-Sun
DS
Kim
Tae Wha
TW
Kim
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005353:Fibronectins / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D007328:Insulin / Q000097:blood; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010766:Phosphorylation / Q000187:drug effects; D011507:Proteinuria / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D020334:Rats, Inbred OLETF; D015398:Signal Transduction / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D008063:Thioctic Acid / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000410:Alanine Transaminase; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D001786:Blood Glucose; D002784:Cholesterol; D005230:Fatty Acids, Nonesterified; D005353:Fibronectins; D006442:Glycated Hemoglobin; D007328:Insulin; D008315:Malondialdehyde; D008063:Thioctic Acid; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases