Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins

Kirtikar Shukla, Pabitra Bikash Pal, Himangshu Sonowal, Satish Srivastava, Kota Ramana

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We have shown earlier that pretreatment of cultured cells with aldose reductase (AR) inhibitors prevents hyperglycemia-induced mitogenic and proinflammatory responses. However, the effects of AR inhibitors on Nrf2-mediated anti-inflammatory responses have not been elucidated yet. We have investigated how AR inhibitor fidarestat protects high glucose-(HG-) induced cell viability changes by increasing the expression of Nrf2 and its dependent phase II antioxidant enzymes. Fidarestat pretreatment prevents HG (25 mM)-induced Thp1 monocyte viability. Further, treatment of Thp1 monocytes with fidarestat caused a time-dependent increase in the expression as well as the DNA-binding activity of Nrf2. In addition, fidarestat augmented the HG-induced Nrf2 expression and activity and also upregulated the expression of Nrf2-dependent proteins such as hemeoxygenase-1 (HO1) and NQO1 in Thp1 cells. Similarly, treatment with AR inhibitor also induced the expression of Nrf2 and HO1 in STZ-induced diabetic mice heart and kidney tissues. Further, AR inhibition increased the HG-induced expression of antioxidant enzymes such as SOD and catalase and activation of AMPK-α1 in Thp1 cells. Our results thus suggest that pretreatment with AR inhibitor prepares the monocytes against hyperglycemic stress by overexpressing the Nrf2-dependent antioxidative proteins.

Original languageEnglish (US)
Article number6785852
JournalJournal of Diabetes Research
Volume2017
DOIs
StatePublished - 2017

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Aldehyde Reductase
Antioxidants
Monocytes
Proteins
Heme Oxygenase-1
AMP-Activated Protein Kinases
Enzymes
Hyperglycemia
Catalase
Cultured Cells
Cell Survival
Anti-Inflammatory Agents
Kidney
Glucose
fidarestat
DNA

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins. / Shukla, Kirtikar; Pal, Pabitra Bikash; Sonowal, Himangshu; Srivastava, Satish; Ramana, Kota.

In: Journal of Diabetes Research, Vol. 2017, 6785852, 2017.

Research output: Contribution to journalArticle

Shukla, Kirtikar ; Pal, Pabitra Bikash ; Sonowal, Himangshu ; Srivastava, Satish ; Ramana, Kota. / Aldose Reductase Inhibitor Protects against Hyperglycemic Stress by Activating Nrf2-Dependent Antioxidant Proteins. In: Journal of Diabetes Research. 2017 ; Vol. 2017.
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