High glucose-induced inhibition of ?-methyl-D-glucopyranoside uptake is mediated by protein kinase C-dependent activation of arachidonic acid release in primary cultured rabbit renal proximal tubule cells

Han, Ho Jae; Choi, Hyunju; Park, Soo-Hyun

doi:10.1002/(sici)1097-4652(200006)183:3<355::aid-jcp8>3.0.co;2-y

Cited by 14 publications

(10 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…33). Recent reports including our works suggest that the activity of SGLT is related to the development of diabetic nephropathy (15,16,29). ANG II also has been reported to be involved in the onset of diabetic nephropathy (5).…”

mentioning

confidence: 68%

“…32), and 3) the concentration of ANG II is increased in diabetic animals (46). Recently, we have demonstrated that high glucose inhibited ␣-MG uptake in PTCs (15,16). Others have demonstrated that high glucose resulted in a reduction of the expression and activity of SGLTs (23) and that SGLT activity was decreased in brushborder membrane vesicles of diabetic rats (19).…”

Section: Discussionmentioning

confidence: 98%

See 1 more Smart Citation

Signaling cascade of ANG II-induced inhibition of α-MG uptake in renal proximal tubule cells

Han

Park

Lee

2004

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

ANG II and Na+-glucose cotransporter have been reported to be associated with the onset of diverse renal diseases. However, the effect of ANG II on Na+-glucose cotransporter activity was not elucidated. The effects of ANG II on alpha-methyl-D-[14C]glucopyranoside (alpha-MG) uptake and its related signal pathways were examined in the primary cultured rabbit renal proximal tubule cells (PTCs). ANG II (>2 h; >10(-9) M) inhibited alpha-MG uptake in a time- and concentration-dependent manner and decreased the protein level of Na+-glucose cotransporters, the expression of which was abrogated by both actinomycin D and cycloheximide exposure. ANG II-induced inhibition of alpha-MG uptake was blocked by losartan, an ANG II type 1 (AT1) receptor blocker, but not by PD-123319, an ANG II type 2 receptor blocker. ANG II-induced inhibition of alpha-MG uptake was blocked by genistein, herbimycin A [tyrosine kinase (TK) inhibitors], mepacrine, and AACOCF3 (phospholipase A2 inhibitors), suggesting the role of TK phosphorylation and arachidonic acid (AA). Indeed, ANG II increased AA release, which was blocked by losartan or TK inhibitors. The effects of ANG II on AA release and alpha-MG uptake also were abolished by staurosporine and bisindolylmaleimide I (protein kinase C inhibitors) or PD-98059 (p44/42 MAPK inhibitor), but not SB-203580 (p38 MAPK inhibitor), respectively. Indeed, ANG II increased p44/42 MAPK activity. ANG II-induced activation of p44/42 MAPK was blocked by staurosporine. In conclusion, ANG II inhibited alpha-MG uptake via PKC-MAPK-cPLA2 signal cascade through the AT1 receptor in the PTCs.

show abstract

mentioning

confidence: 68%

Section: Discussionmentioning

confidence: 98%

Signaling cascade of ANG II-induced inhibition of α-MG uptake in renal proximal tubule cells

Han

Park

Lee

2004

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…These multiple isotypes of PKC have variable tissue distributions, biochemical regulations, and physiological functions that at times are cell specific. Many of them, including, ␣, ␤, ␦, ε, and , have been reported to modulate hyperglycemia-induced renal injury, consequentially leading to fibrosis (21,61). In addition, it has been shown that the activity of PKC parallels that of TGF-␤ and fibronectin protein expression, which can be blocked by inhibition of PKC (19,52).…”

Section: Discussionmentioning

confidence: 99%

Pathobiology of renal-specific oxidoreductase/myo-inositol oxygenase in diabetic nephropathy: its implications in tubulointerstitial fibrosis

Xie

Sun

Oates

et al. 2010

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Xie P, Sun L, Oates PJ, Srivastava SK, Kanwar YS. Pathobiology of renal-specific oxidoreductase/myo-inositol oxygenase in diabetic nephropathy: its implications in tubulointerstitial fibrosis. Am J Physiol Renal Physiol 298: F1393-F1404, 2010. First published March 24, 2010 doi:10.1152/ajprenal.00137.2010.-Renal-specific oxido-reductase/myoinositol oxygenase (RSOR/MIOX) is expressed in renal tubules. It catabolizes myo-inositol and its expression is increased in diabetic mice and in LLC-PK 1 cells under high-glucose ambience. Aldose reductase (AR) is another aldo-keto reducase that is expressed in renal tubules. It regulates the polyol pathway and plays an important role in glucose metabolism, osmolyte regulation, and ECM pathobiology via the generation of advanced glycation end products, reactive oxygen species, and activation of transforming growth factor (TGF)-␤. In view of the similarities between AR and RSOR/MIOX, the pathobiology of RSOR/MIOX and some of the cellular pathways affected by its overexpression were investigated. An increased expression of fibronectin was noted by transfection of LLC-PK 1 cells with pcDNA3.1-RSOR/MIOX. Similar changes were observed in LLC-PK 1 cells under high-glucose ambience, and they were notably lessened by RSOR/MIOX-small interfering (si) RNA treatment. The changes in tubulointerstitial fibronectin expression were also observed in the kidneys of db/db mice having high levels of RSOR. The pcDNA3.1-RSOR/MIOX transfectants had an increased NADH/NAD ϩ ratio, PKC and TGF-␤ activity, Raf1:Ras association, and p-ERK phosphorylation. These changes were significantly reduced by the inhibitors of PKC, aldose reductase, Ras farnesylation, and MEK1. Similar increases in various the above-noted parameters were observed under high-glucose ambience. Such changes were partially reversed with RSOR-siRNA treatment. Expression of Ecadherin and vimentin paralleled in cells overexpressing RSOR/ MIOX or subjected to high-glucose ambience. These studies suggest that RSOR/MIOX modulates various downstream pathways affected by high-glucose ambience, and conceivably it plays a role in the pathobiology of tubulointerstitium in diabetic nephropathy.fibronectin; db/db mice; sorbinil DIABETES MELLITUS IS A COMMON metabolic disorder in which hyperglycemia afflicts injury on multiple organ systems in humans, and frequent lesions that have been well described include diabetic microangiopathy, neuropathy, retinopathy, and nephropathy (6,33,47,54). The changes in the kidney occur in more than one-third of the patients with diabetes mellitus, and they have been exhaustively described in the literature (27,46,51,53,57,62). The hyperglycemia-induced renal changes may be acute and reversible or chronic and irreversible in nature, and these kidney lesions may serve as a prototypical example that would be applicable to other mammalian organ systems. The acute metabolic changes include increased activity of the polyol pathway, altered redox state of pyridine nucleotides (NADPH:NADP ϩ and NADH:NAD ϩ ratios), pert...

show abstract

“…It was demonstrated that high glucose inhibits the activity of SGLT by increasing the AA release, which is regulated by PKC-oxidative stress (Figure 2). 67 Therefore, the PKC-induced activation of PLA 2 provides a novel mechanism that directly implicates hyperglycemia in the inhibition of the glucose reabsorption of PTCs. This abnormal glucose handling in the proximal tubule might play an important role in the development of diabetic nephropathy, even though renal PTCs do not appear to be primary targets for diabetic injury.…”

Section: High Glucose and Sgltsmentioning

confidence: 99%

“…74 Therefore, ANG II is involved in the high glucoseinduced inhibition of a-MG uptake through an increase in ANG II by high glucose levels. 67,71,98 Mice overexpressing a dominant-negative isoform of the EGFR were protected from renal lesions such as glomerulosclerosis, tubular atrophy, fibrosis, mononuclear cell infiltration during chronic ANG II infusion, suggesting that EGFR plays a key role in ANG II-dependent EGFR transactivation in renal pathogenesis. 99 Many of the deleterious effects of ANG II in the cardiovascular system are mediated through the matrix metalloproteinase-dependent activation of the EGFR.…”

mentioning

confidence: 99%

Regulatory mechanisms of Na + /glucose cotransporters in renal proximal tubule cells

Lee

Han

2007

Kidney International

153

View full text Add to dashboard Cite

Glucose is a key fuel and an important metabolic substrate in mammals. Renal proximal tubular cells (PTCs) not only reabsorb filtered glucose but are also believed to play a role in the glucotoxicity associated with renal pathogenesis, such as in diabetes. The proximal tubule environment is where 90% of the filtered glucose is reabsorbed by the low-affinity/high-capacity Na(+)/glucose cotransporter 2 (SGLT2) and facilitated diffusion glucose transporter 2 (GLUT2). Both active and facilitative glucose transporters have distinct distribution profiles along the proximal tubule related to their particular kinetic characteristics. A number of mechanisms contribute to the changes in the cellular functions, which occur in response to exposure to various endogenous factors. Hyperglycemia was reported to regulate the renal SGLT activities through the reactive oxygen species-nuclear factor-kappaB pathways, which suggests that the transcellular glucose uptake within the PTCs contribute to the development of diabetic-like nephropathy. Angiotensin II (ANG II) plays an important role in its development through epidermal growth factor receptor (EGFR) transactivation. Therefore, a combination of high glucose, ANG II, and EGF are involved in diabetic-like nephropathy by regulating the SGLT activity. In addition, endogenously enhanced SGLTs have a cytoprotective function. The renal proximal tubules play a major role in regulating the plasma glucose levels, and there is increasing interest in the renal glucose transporters on account of their potential implications in the treatment of various conditions including diabetes mellitus.

show abstract

High glucose-induced inhibition of ?-methyl-D-glucopyranoside uptake is mediated by protein kinase C-dependent activation of arachidonic acid release in primary cultured rabbit renal proximal tubule cells

Cited by 14 publications

References 41 publications

Signaling cascade of ANG II-induced inhibition of α-MG uptake in renal proximal tubule cells

Signaling cascade of ANG II-induced inhibition of α-MG uptake in renal proximal tubule cells

Pathobiology of renal-specific oxidoreductase/myo-inositol oxygenase in diabetic nephropathy: its implications in tubulointerstitial fibrosis

Regulatory mechanisms of Na + /glucose cotransporters in renal proximal tubule cells

Contact Info

Product

Resources

About