Catalase prevents maternal diabetes-induced perinatal programming via the Nrf2-HO-1 defense system

Shiao Ying Chang, Yun-Wen Chen, Xin Ping Zhao, Isabelle Chenier, Stella Tran, Alexandre Sauvé, Julie R. Ingelfinger, Shao Ling Zhang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

We investigated whether overexpression of catalase (CAT) in renal proximal tubular cells (RPTCs) could prevent the programming of hypertension and kidney disease in the offspring of dams with maternal diabetes. Male offspring of nondiabetic and diabetic dams from two transgenic (Tg) lines (Hoxb7-green fluorescent protein [GFP]-Tg [controls] and Hoxb7/CAT-GFP-Tg, which overexpress CAT in RPTCs) were studied from the prenatal period into adulthood. Nephrogenesis, systolic blood pressure, renal hyperfiltration, kidney injury, and reactive oxygen species (ROS) generation were assessed. Gene expression of transforming growth factorβ1 (TGFβ1), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and heme oxygenase-1 (HO-1) was tested in both in vitro and in vivo studies. Renal dysmorphogenesis was observed in offspring of Hoxb7-GFP-Tg dams with severe maternal diabetes; the affected male offspring displayed higher renal ROS generation and developed hypertension and renal hyperfiltration as well as renal injury with heightened TGFβ1 expression in adulthood. These changes were ameliorated in male offspring of diabetic Hoxb7/ CAT-GFP-Tg dams via the Nrf2-HO-1 defense system. CAT promoted Nrf2 nuclear translocation and HO-1 gene expression, seen in both in vitro and in vivo studies. In conclusion, CAT overexpression in the RPTCs ameliorated maternal diabetes-induced perinatal programming, mediated, at least in part, by triggering the Nrf2-HO-1 defense system.

Original languageEnglish
Pages (from-to)2565-2574
Number of pages10
JournalDiabetes
Volume61
Issue number10
DOIs
Publication statusPublished - 2012 Oct 1

Fingerprint

Heme Oxygenase-1
Catalase
Mothers
Kidney
Green Fluorescent Proteins
Reactive Oxygen Species
Blood Pressure
Gene Expression
Renal Hypertension
Wounds and Injuries
Kidney Diseases
Growth
Hypertension

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chang, S. Y., Chen, Y-W., Zhao, X. P., Chenier, I., Tran, S., Sauvé, A., ... Zhang, S. L. (2012). Catalase prevents maternal diabetes-induced perinatal programming via the Nrf2-HO-1 defense system. Diabetes, 61(10), 2565-2574. https://doi.org/10.2337/db12-0248
Chang, Shiao Ying ; Chen, Yun-Wen ; Zhao, Xin Ping ; Chenier, Isabelle ; Tran, Stella ; Sauvé, Alexandre ; Ingelfinger, Julie R. ; Zhang, Shao Ling. / Catalase prevents maternal diabetes-induced perinatal programming via the Nrf2-HO-1 defense system. In: Diabetes. 2012 ; Vol. 61, No. 10. pp. 2565-2574.
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abstract = "We investigated whether overexpression of catalase (CAT) in renal proximal tubular cells (RPTCs) could prevent the programming of hypertension and kidney disease in the offspring of dams with maternal diabetes. Male offspring of nondiabetic and diabetic dams from two transgenic (Tg) lines (Hoxb7-green fluorescent protein [GFP]-Tg [controls] and Hoxb7/CAT-GFP-Tg, which overexpress CAT in RPTCs) were studied from the prenatal period into adulthood. Nephrogenesis, systolic blood pressure, renal hyperfiltration, kidney injury, and reactive oxygen species (ROS) generation were assessed. Gene expression of transforming growth factorβ1 (TGFβ1), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and heme oxygenase-1 (HO-1) was tested in both in vitro and in vivo studies. Renal dysmorphogenesis was observed in offspring of Hoxb7-GFP-Tg dams with severe maternal diabetes; the affected male offspring displayed higher renal ROS generation and developed hypertension and renal hyperfiltration as well as renal injury with heightened TGFβ1 expression in adulthood. These changes were ameliorated in male offspring of diabetic Hoxb7/ CAT-GFP-Tg dams via the Nrf2-HO-1 defense system. CAT promoted Nrf2 nuclear translocation and HO-1 gene expression, seen in both in vitro and in vivo studies. In conclusion, CAT overexpression in the RPTCs ameliorated maternal diabetes-induced perinatal programming, mediated, at least in part, by triggering the Nrf2-HO-1 defense system.",
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Chang, SY, Chen, Y-W, Zhao, XP, Chenier, I, Tran, S, Sauvé, A, Ingelfinger, JR & Zhang, SL 2012, 'Catalase prevents maternal diabetes-induced perinatal programming via the Nrf2-HO-1 defense system', Diabetes, vol. 61, no. 10, pp. 2565-2574. https://doi.org/10.2337/db12-0248

Catalase prevents maternal diabetes-induced perinatal programming via the Nrf2-HO-1 defense system. / Chang, Shiao Ying; Chen, Yun-Wen; Zhao, Xin Ping; Chenier, Isabelle; Tran, Stella; Sauvé, Alexandre; Ingelfinger, Julie R.; Zhang, Shao Ling.

In: Diabetes, Vol. 61, No. 10, 01.10.2012, p. 2565-2574.

Research output: Contribution to journalArticle

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AU - Chang, Shiao Ying

AU - Chen, Yun-Wen

AU - Zhao, Xin Ping

AU - Chenier, Isabelle

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AU - Sauvé, Alexandre

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AU - Zhang, Shao Ling

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