α, βI, βII, δ, and ε Protein Kinase C Isoforms and Compound Activity in the Sciatic Nerve of Normal and Diabetic Rats

Borghini, Isabelle; Ania-Lahuerta, Aldonza; Regazzi, Romano; Ferrari, Giovanna; Gjinovci, Asllan; Wollheim, Claes B.; Pralong, William

doi:10.1046/j.1471-4159.1994.62020686.x

Cited by 59 publications

(19 citation statements)

References 47 publications

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“…PKC contributes to diabetic neuropathy by a neurovascular mechanism such as blood flow and conduction velocity. Immunochemical analysis demonstrated the presence of PKC-α, -β1, -β2, -γ, PKC-δ and -ε isoforms in nerve 108, 109. A previous report demonstrated a reduction of PKC activity by direct measurement of sciatic nerve tissues in streptozotocin diabetic rats 110.…”

Section: Pkc Activation: Animal Model Studiesmentioning

confidence: 74%

Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications

Geraldes

King

2010

Circulation Research

777

588

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Key Words: protein kinase C Ⅲ vascular cell biology Ⅲ diabetes Ⅲ cardiovascular diseases D iabetes currently affects nearly 170 million people worldwide and this number will double by 2030, affecting both developed and developing countries. 1 The major cause complications in diabetic patients is complications, which are the result of interactions among systemic metabolic abnormalities such as hyperglycemia, dyslipidemia, genetic and epigenetic modulators and local tissue responses to toxic metabolites. Complications involve large vessel obstructions, such as coronary artery diseases, atherosclerosis, and peripheral vascular diseases, and microvascular pathologies, including retinopathy, nephropathy, and neuropathy. Hyperglycemia is one of the major systemic risk factors for diabetic complications. The Diabetes Control and Complications Trial (DCCT) in type 1 diabetes 2 and the United Kingdom Pro-

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Section: Pkc Activation: Animal Model Studiesmentioning

confidence: 74%

Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications

Geraldes

King

2010

Circulation Research

777

588

View full text Add to dashboard Cite

show abstract

“…For this reason, PKC activity was measured in vitro after many procedures, as it might cleave the binding of PKC-b inhibitor, resulting in no inhibition of PKC activity. Furthermore, separate measurement of endoneural and perineural vascular tissues may be required to evaluate nerve PKC activity [43,44].…”

Section: Discussionmentioning

confidence: 99%

Novel protein kinase C‐β isoform selective inhibitor JTT‐010 ameliorates both hyper‐ and hypoalgesia in streptozotocin‐ induced diabetic rats

Sasase

Yamada

Sakoda

et al. 2004

Diabetes Obesity Metabolism

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“…Together with the observation that both DRG neurons and peripheral nerves are directly modulated by PKC, these findings may be compatible with the notion that LY333531 would have a beneficial effect on hyperalgesia by directly affecting the nociceptive threshold at the peripheral nerve level. With respect to the activity of PKC and the presence of its isoforms in diabetic nerves, it remains controversial whether PKC activity in diabetic nerves is reduced (37,38), unchanged (7,39), or increased (40), and it also remains unclear which isoform is altered in diabetic nerves. Our results that the ratio of membrane to cytosol PKC␤II activity was significantly higher in diabetic than in control nerves, and that LY333531significantly reduced phosphorylated PKC␤II, may support increased PKC␤ II activity of DRG neurons and the inhibitory effect of LY333531 on PKC␤II activity of DRG neurons in diabetes.…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase Cβ Selective Inhibitor LY333531 Attenuates Diabetic Hyperalgesia Through Ameliorating cGMP Level of Dorsal Root Ganglion Neurons

et al. 2003

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Streptozocin (STZ)-induced diabetic rats show hyperalgesia that is partially attributed to altered protein kinase C (PKC) activity. Both attenuated neuronal nitric oxide synthase (nNOS)-cGMP system and tetrodotoxin-resistant (TTX-R) Na channels in dorsal root ganglion neurons may be involved in diabetic hyperalgesia. We examined whether PKC␤ inhibition ameliorates diabetic hyperalgesia and, if so, whether the effect is obtained through action on neurons by testing nociceptive threshold in normal and STZ-induced diabetic rats treated with or without PKC␤-selective inhibitor LY333531 (LY) and by assessing the implication of LY in either nNOS-cGMP system or TTX-R Na channels of isolated dorsal root ganglion neurons. The decreased nociceptive threshold in diabetic rats was improved either after 4 weeks of LY treatment or with a single intradermal injection into the footpads. The treatment of LY for 6 weeks significantly decreased p-PKC␤ and ameliorated a decrease in cGMP content in dorsal root ganglia of diabetic rats. The latter effect was confirmed in ex vivo condition. The treatment with NO donor for 4 weeks also normalized both diabetic hyperalgesia and decreased cGMP content in dorsal root ganglions. The expressions of nNOS and TTX-R Na channels were not changed with LY treatment. These results suggest that LY is effective for treating diabetic hyperalgesia through ameliorating the decrease in the nNOS-cGMP system.

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α, βI, βII, δ, and ε Protein Kinase C Isoforms and Compound Activity in the Sciatic Nerve of Normal and Diabetic Rats

Cited by 59 publications

References 47 publications

Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications

Activation of Protein Kinase C Isoforms and Its Impact on Diabetic Complications

Novel protein kinase C‐β isoform selective inhibitor JTT‐010 ameliorates both hyper‐ and hypoalgesia in streptozotocin‐ induced diabetic rats

Protein Kinase Cβ Selective Inhibitor LY333531 Attenuates Diabetic Hyperalgesia Through Ameliorating cGMP Level of Dorsal Root Ganglion Neurons

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