JOURNAL ARTICLE
REVIEW

Pathogenesis of diabetic nephropathy: the role of oxidative stress and protein kinase C

H Ha, K H Kim
Diabetes Research and Clinical Practice 1999, 45 (2-3): 147-51
10588367
Hyperglycemia, a well recognized pathogenetic factor of long-term complications in diabetes mellitus, not only generates more reactive oxygen species but also attenuates antioxidative mechanisms through glycation of the scavenging enzymes. Therefore, oxidative stress has been considered to be a common pathogenetic factor of the diabetic complications including nephropathy. A causal relationship between oxidative stress and diabetic nephropathy has been established by observations that (1) lipid peroxides and 8-hydroxydeoxyguanosine, indices of oxidative tissue injury, were increased in the kidneys of diabetic rats with albuminuria; (2) high glucose directly increases oxidative stress in glomerular mesangial cells, a target cell of diabetic nephropathy; (3) oxidative stress induces mRNA expression of TGF-beta1 and fibronectin which are the genes implicated in diabetic glomerular injury, and (4) inhibition of oxidative stress ameliorates all the manifestations associated with diabetic nephropathy. Proposed mechanisms involved in oxidative stress associated with hyperglycemia are glucose autooxidation, the formation of advanced glycosylation end products, and metabolic stress resulting from hyperglycemia. Since the inhibition of protein kinase C (PKC) effectively blocks not only phorbol ester-induced but also high glucose- and H2O2-induced fibronectin production, the activation of PKC under diabetic conditions may also have a modulatory role in oxidative stress-induced renal injury in diabetes mellitus.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
10588367
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"