scholarly journals Effect of type 1 diabetes on protein kinase C (PKC) in rat renal medullary thick ascending limb

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
JING YANG ◽  
Jennifer S. Pollock ◽  
Pamela K. Carmines
Keyword(s):  
Type 1 Diabetes ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Thick Ascending Limb ◽  
Medullary Thick Ascending Limb ◽  
Kinase C

ANG II controls Na+-K+( NH 4 + )-2Cl−cotransport via 20-HETE and PKC in medullary thick ascending limb

1998 ◽  
Vol 274 (4) ◽  
pp. C1047-C1056 ◽  
Author(s):  
Hassane Amlal ◽  
Christian LeGoff ◽  
Catherine Vernimmen ◽  
Manoocher Soleimani ◽  
Michel Paillard ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Phospholipase C ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Diacylglycerol Lipase ◽  
Medullary Thick Ascending Limb ◽  
Kinase C ◽  
Cell Ph ◽  
Cytochrome P 450

Cell pH was monitored in medullary thick ascending limbs to determine effects of ANG II on Na+-K+([Formula: see text])-2Cl−cotransport. ANG II at 10−16to 10−12 M inhibited 30–50% ( P < 0.005), but higher ANG II concentrations were stimulatory compared with the 10−12 M ANG II level cotransport activity; eventually, 10−6 M ANG II stimulated 34% cotransport activity ( P < 0.003). Inhibition by 10−12M ANG II was abolished by phospholipase C (PLC), diacylglycerol lipase, or cytochrome P-450-dependent monooxygenase blockade; 10−12 M ANG II had no effect additive to inhibition by 20-hydroxyeicosatetranoic acid (20-HETE). Stimulation by 10−6 M ANG II was abolished by PLC and protein kinase C (PKC) blockade and was partially suppressed when the rise in cytosolic Ca2+ was prevented. All ANG II effects were abolished by DUP-753 (losartan) but not by PD-123319. Thus ≤10−12 M ANG II inhibits via 20-HETE, whereas ≥5 × 10−11 M ANG II stimulates via PKC Na+-K+([Formula: see text])-2Cl−cotransport; all ANG II effects involve AT1 receptors and PLC activation.

scholarly journals Effect of Protein Kinase C  Inhibition on Renal Hemodynamic Function and Urinary Biomarkers in Humans With Type 1 Diabetes: A Pilot Study

Diabetes Care ◽  
2008 ◽  
Vol 32 (1) ◽  
pp. 91-93 ◽  
Author(s):  
D. Z.I. Cherney ◽  
A. Konvalinka ◽  
B. Zinman ◽  
E. P. Diamandis ◽  
A. Soosaipillai ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Protein Kinase C ◽  
Pilot Study ◽  
Protein Kinase ◽  
Urinary Biomarkers ◽  
Kinase C ◽  
Renal Hemodynamic ◽  
Hemodynamic Function

scholarly journals Whole-Genome Sequencing of Finnish Type 1 Diabetic Siblings Discordant for Kidney Disease Reveals DNA Variants associated with Diabetic Nephropathy

2020 ◽  
Vol 31 (2) ◽  
pp. 309-323 ◽  
Author(s):  
Jing Guo ◽  
Owen J. L. Rackham ◽  
Niina Sandholm ◽  
Bing He ◽  
Anne-May Österholm ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Diabetic Nephropathy ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Kidney Disease ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Replication Cohort ◽  
Kinase C

BackgroundSeveral genetic susceptibility loci associated with diabetic nephropathy have been documented, but no causative variants implying novel pathogenetic mechanisms have been elucidated.MethodsWe carried out whole-genome sequencing of a discovery cohort of Finnish siblings with type 1 diabetes who were discordant for the presence (case) or absence (control) of diabetic nephropathy. Controls had diabetes without complications for 15–37 years. We analyzed and annotated variants at genome, gene, and single-nucleotide variant levels. We then replicated the associated variants, genes, and regions in a replication cohort from the Finnish Diabetic Nephropathy study that included 3531 unrelated Finns with type 1 diabetes.ResultsWe observed protein-altering variants and an enrichment of variants in regions associated with the presence or absence of diabetic nephropathy. The replication cohort confirmed variants in both regulatory and protein-coding regions. We also observed that diabetic nephropathy–associated variants, when clustered at the gene level, are enriched in a core protein-interaction network representing proteins essential for podocyte function. These genes include protein kinases (protein kinase C isoforms ε and ι) and protein tyrosine kinase 2.ConclusionsOur comprehensive analysis of a diabetic nephropathy cohort of siblings with type 1 diabetes who were discordant for kidney disease points to variants and genes that are potentially causative or protective for diabetic nephropathy. This includes variants in two isoforms of the protein kinase C family not previously linked to diabetic nephropathy, adding support to previous hypotheses that the protein kinase C family members play a role in diabetic nephropathy and might be attractive therapeutic targets.

PGE2 reverses AVP inhibition of HCO3- absorption in rat MTAL by activation of protein kinase C

1996 ◽  
Vol 270 (6) ◽  
pp. F978-F985 ◽  
Author(s):  
D. W. Good
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Absorption Rate ◽  
Thick Ascending Limb ◽  
Camp Production ◽  
Medullary Thick Ascending Limb ◽  
Kinase C ◽  
Chelerythrine Chloride ◽  
Dependent Mechanism

In the medullary thick ascending limb (MTAL) of the rat, prostaglandin E2 (PGE2) reverses inhibition of HCO3- absorption (JHCO3) by arginine vasopressin (AVP) by inhibiting AVP-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production. To determine whether this regulation by PGE2 involves protein kinase C (PKC), MTAL segments were perfused in vitro with physiological solutions containing 25 mM HCO3- (pH 7.4). With 10(-10) MAVP in the bath, addition of 10(-6) M PGE2 to the bath increased JHCO3 from 7.8 +/- 0.4 to 13.0 +/- 1.1 pmol.min-1.mm-1 (P < 0.01). This effect was blocked completely by pretreatment with the PKC inhibitors staurosporine or chelerythrine chloride (10(-7) M in the bath). With both AVP and PGE2 in the bath, addition of staurosporine or chelerythrine to the bath decreased JHCO3 from 12.2 +/- 1.1 to 7.3 +/- 0.6 pmol.min-1.mm-1 (P < 0.005). Neither staurosporine nor chelerythrine affected JHCO3 under basal conditions or in the presence of AVP alone. With AVP in the bath, addition of phorbol 12-myristate 13-acetate (PMA, 10(-6) M) to the bath increased JHCO3 from 5.0 +/- 0.5 to 9.1 +/- 1.0 pmol.min-1.mm-1 (P < 0.01). Similar to PGE2, PMA had no effect on JHCO3 in the absence of AVP or in the presence of 10(-6) M bath forskolin. The effect of PMA to stimulate JHCO3 in the presence of AVP was abolished by pretreatment with pertussis toxin (2 x 10(-11) M). We conclude that 1) PGE2 reverses AVP inhibition of HCO3- absorption by activation of PKC, 2) PKC likely increases JHCO3 by inhibiting AVP-stimulated cAMP production via a Gi-dependent mechanism, and 3) PKC activity has no influence on basal HCO3- absorption rate.

Sign in / Sign up

Export Citation Format

Share Document