Effect of heat-shock protein B7 on oxidative stress in adipocytes from preruminant calves

Xudong Sun, Xiaobing Li, Hongdou Jia, Juan J Loor, Ryan Bucktrout, Qiushi Xu, Yazhe Wang, Xin Shu, Jihong Dong, Rankun Zuo, Liangyu Yang, Guowen Liu, Xinwei Li

Research output: Contribution to journalArticle

Abstract

Dairy cows with ketosis display excessive lipolysis in adipose tissue. Heat-shock protein B7 (HSPB7), a small heat-shock protein, plays important roles in mediating cytoprotective responses to oxidative stress in rodent adipose tissue. Accordingly, it is assumed that HSPB7 may also play important roles in the antioxidant response in adipose tissue of ketotic cows. Therefore, the aim of this study is to investigate (1) the redox state of adipose tissue in ketotic cows and (2) the role and mechanism of HSPB7 on the regulation of oxidative stress in adipocytes from preruminant calves. An in vivo study consisting of 15 healthy and 15 clinically ketotic cows was performed to harvest subcutaneous adipose tissue and blood samples. In addition, adipocytes isolated from calves were treated with different concentrations of H 2 O 2 (0, 12.5, 25, 50, 100, or 200 μM) for 2 h, transfected with adenovirus-mediated overexpression of HSPB7 for 48 h, or transfected with small interfering RNA of HSPB7 for 48 h followed by exposure to H 2 O 2 (200 μM) for 2 h. Serum concentrations of nonesterified fatty acids and β-hydroxybutyrate were greater in cows with clinical ketosis, whereas serum concentration of glucose was lower. Compared with healthy cows, the malondialdehyde content was greater but the activity of glutathione peroxidase and superoxide dismutase was lower in adipose tissue of clinically ketotic cows. The abundance of HSPB7 and nuclear factor, erythroid 2 like 2 (NFE2L2) was greater in adipose tissue of clinically ketotic cows. In vitro, H 2 O 2 treatment induced the overproduction of reactive oxygen species and malondialdehyde, and inhibited the activity of antioxidant enzymes glutathione peroxidase and superoxide dismutase in adipocytes from preruminant calves. The low concentration of H 2 O 2 (12.5, 25, and 50 μM) increased the abundance of HSPB7 and NFE2L2, but high concentrations of H 2 O 2 (100 or 200 μM) reduced the abundance of HSPB7 and NFE2L2. The overexpression of HSPB7 improved the H 2 O 2 -induced oxidative stress in adipocytes via increasing the abundance of NFE2L2 and its downstream target genes heme oxygenase-1 (HMOX1) and NADH quinone oxidoreductase 1 (NQO1). Knockdown of HSPB7 markedly inhibited the expression of NFE2L2, HMOX1, and NQO1 and further exacerbated H 2 O 2 -induced oxidative stress. Overall, these results indicate that activation of the HSPB7-NFE2L2 pathway increases cellular antioxidant capacity, thereby alleviating oxidative stress in bovine adipocytes.

Original languageEnglish (US)
Pages (from-to)5673-5685
Number of pages13
JournalJournal of Dairy Science
Volume102
Issue number6
DOIs
StatePublished - Jun 2019

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Heat-Shock Proteins
adipocytes
heat shock proteins
Adipocytes
Oxidative Stress
oxidative stress
calves
adipose tissue
Adipose Tissue
cows
heme oxygenase (biliverdin-producing)
Ketosis
Heme Oxygenase-1
Antioxidants
ketosis
Glutathione Peroxidase
oxidoreductases
Malondialdehyde
blood serum
quinones

Keywords

  • HSPB7
  • NFE2L2
  • adipocytes
  • oxidative stress

ASJC Scopus subject areas

  • Food Science
  • Animal Science and Zoology
  • Genetics

Cite this

Effect of heat-shock protein B7 on oxidative stress in adipocytes from preruminant calves. / Sun, Xudong; Li, Xiaobing; Jia, Hongdou; Loor, Juan J; Bucktrout, Ryan; Xu, Qiushi; Wang, Yazhe; Shu, Xin; Dong, Jihong; Zuo, Rankun; Yang, Liangyu; Liu, Guowen; Li, Xinwei.

In: Journal of Dairy Science, Vol. 102, No. 6, 06.2019, p. 5673-5685.

Research output: Contribution to journalArticle

Sun, X, Li, X, Jia, H, Loor, JJ, Bucktrout, R, Xu, Q, Wang, Y, Shu, X, Dong, J, Zuo, R, Yang, L, Liu, G & Li, X 2019, 'Effect of heat-shock protein B7 on oxidative stress in adipocytes from preruminant calves', Journal of Dairy Science, vol. 102, no. 6, pp. 5673-5685. https://doi.org/10.3168/jds.2018-15726
Sun, Xudong ; Li, Xiaobing ; Jia, Hongdou ; Loor, Juan J ; Bucktrout, Ryan ; Xu, Qiushi ; Wang, Yazhe ; Shu, Xin ; Dong, Jihong ; Zuo, Rankun ; Yang, Liangyu ; Liu, Guowen ; Li, Xinwei. / Effect of heat-shock protein B7 on oxidative stress in adipocytes from preruminant calves. In: Journal of Dairy Science. 2019 ; Vol. 102, No. 6. pp. 5673-5685.
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AU - Sun, Xudong

AU - Li, Xiaobing

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AU - Loor, Juan J

AU - Bucktrout, Ryan

AU - Xu, Qiushi

AU - Wang, Yazhe

AU - Shu, Xin

AU - Dong, Jihong

AU - Zuo, Rankun

AU - Yang, Liangyu

AU - Liu, Guowen

AU - Li, Xinwei

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N2 - Dairy cows with ketosis display excessive lipolysis in adipose tissue. Heat-shock protein B7 (HSPB7), a small heat-shock protein, plays important roles in mediating cytoprotective responses to oxidative stress in rodent adipose tissue. Accordingly, it is assumed that HSPB7 may also play important roles in the antioxidant response in adipose tissue of ketotic cows. Therefore, the aim of this study is to investigate (1) the redox state of adipose tissue in ketotic cows and (2) the role and mechanism of HSPB7 on the regulation of oxidative stress in adipocytes from preruminant calves. An in vivo study consisting of 15 healthy and 15 clinically ketotic cows was performed to harvest subcutaneous adipose tissue and blood samples. In addition, adipocytes isolated from calves were treated with different concentrations of H 2 O 2 (0, 12.5, 25, 50, 100, or 200 μM) for 2 h, transfected with adenovirus-mediated overexpression of HSPB7 for 48 h, or transfected with small interfering RNA of HSPB7 for 48 h followed by exposure to H 2 O 2 (200 μM) for 2 h. Serum concentrations of nonesterified fatty acids and β-hydroxybutyrate were greater in cows with clinical ketosis, whereas serum concentration of glucose was lower. Compared with healthy cows, the malondialdehyde content was greater but the activity of glutathione peroxidase and superoxide dismutase was lower in adipose tissue of clinically ketotic cows. The abundance of HSPB7 and nuclear factor, erythroid 2 like 2 (NFE2L2) was greater in adipose tissue of clinically ketotic cows. In vitro, H 2 O 2 treatment induced the overproduction of reactive oxygen species and malondialdehyde, and inhibited the activity of antioxidant enzymes glutathione peroxidase and superoxide dismutase in adipocytes from preruminant calves. The low concentration of H 2 O 2 (12.5, 25, and 50 μM) increased the abundance of HSPB7 and NFE2L2, but high concentrations of H 2 O 2 (100 or 200 μM) reduced the abundance of HSPB7 and NFE2L2. The overexpression of HSPB7 improved the H 2 O 2 -induced oxidative stress in adipocytes via increasing the abundance of NFE2L2 and its downstream target genes heme oxygenase-1 (HMOX1) and NADH quinone oxidoreductase 1 (NQO1). Knockdown of HSPB7 markedly inhibited the expression of NFE2L2, HMOX1, and NQO1 and further exacerbated H 2 O 2 -induced oxidative stress. Overall, these results indicate that activation of the HSPB7-NFE2L2 pathway increases cellular antioxidant capacity, thereby alleviating oxidative stress in bovine adipocytes.

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