Relationship between aldose reductase enzyme and the signaling pathway of protein kinase C in an in vitro diabetic retinopathy model


Sarikaya M., YAZIHAN N., Evcimen N. D.

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, cilt.98, sa.4, ss.243-251, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 98 Sayı: 4
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1139/cjpp-2019-0211
  • Dergi Adı: CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, Applied Science & Technology Source, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, SportDiscus, Veterinary Science Database
  • Sayfa Sayıları: ss.243-251
  • Anahtar Kelimeler: aldose reductase, protein kinase C, hyperglycemia, oxidative stress, retinopathy, POLY(ADP-RIBOSE) POLYMERASE ACTIVATION, OXIDATIVE-NITROSATIVE STRESS, PIGMENTED EPITHELIAL-CELLS, HIGH-GLUCOSE, GENE-EXPRESSION, POLYOL PATHWAY, MECHANISMS, DIACYLGLYCEROL, COMPLICATIONS, PATHOGENESIS
  • Ankara Üniversitesi Adresli: Evet

Özet

Protein kinase C (PKC) and aldose reductase (AR) enzyme activities are increased in diabetes and complications are include retinopathy, nephropathy, and neuropathy. However, the relationship between PKC and AR and the underlying molecular mechanisms is still unclear. We aimed to evaluate the relationship between these two enzymes and clarify the underlying molecular mechanisms by the related signaling molecules. The effects of hyperglycemia and oxidative stress on AR and PKC enzymes and the signaling molecules such as nuclear factor-kappa B (NF-kappa B), inhibitor kappa B-alpha (IkB-alpha), total c-Jun, phospho c-Jun, and stress-activated protein kinases (SAPK)/Jun amino-terminal kinases (JNK) were evaluated in human retinal pigment epithelial cells (ARPE-19). AR, PKC protein levels, and related signaling molecules increased with hyperglycemia and oxidative stress. The AR inhibitor sorbinil decreased PKC expression and activity and all signaling molecule protein levels. Increased AR expression during hyperglycemia and oxidative stress was found to be correlated with the increase in PKC expression and activity in both conditions. Decreased expression and activity of PKC and the protein levels of related signaling molecules with the AR inhibitor sorbinil showed that AR enzyme may play a key role in the expression of PKC enzyme and oxidative stress during diabetes.