Top

Research Article

Split Viewer

Mol. Cells 2011; 31(3): 209-215

Published online March 31, 2011

https://doi.org/10.1007/s10059-011-0028-4

© The Korean Society for Molecular and Cellular Biology

p-Hydroxybenzyl Alcohol Prevents Brain Injury and Behavioral Impairment by Activating Nrf2, PDI, and Neurotrophic Factor Genes in a Rat Model of Brain Ischemia

Kyung-Yoon Kam1,2,3, Seong Jin Yu4, Nahee Jeong4, Jeong Hwa Hong5, Angela M. A. Anthony Jalin4, Sungja Lee1, Yong Won Choi1, Chae Kwan Lee6, and Sung Goo Kang2,4,*

1Department of Occupational Therapy, Inje University, Gimhae 621-749, Korea, 2FIRST Research Group, Inje University, Gimhae 621-749, Korea, 3Institute of Aged Life Redesign, Inje University, Gimhae 621-749, Korea, 4School of Biological Sciences, Inje University, Gimhae 621-749, Korea, 5School of Food and Life Science , Inje University, Gimhae 621-749, Korea, 6Institute of Environmental and Occupational Medicine, Department of Occupational and Environmental Medicine, Busan Paik Hospital, Inje University, Busan 614-735, Korea

Correspondence to : *Correspondence: biosgkan@inje.ac.kr

Received: May 3, 2010; Revised: November 30, 2010; Accepted: December 8, 2010

Abstract

The therapeutic goal in treating cerebral ischemia is to reduce the extent of brain injury and thus minimize neurological impairment. We examined the effects of p-hydro-xybenzyl alcohol (HBA), an active component of Gastrodia elata Blume, on transient focal cerebral ische-mia-induced brain injury with respect to the involvement of protein disulphide isomerase (PDI), nuclear factor-E2-related factor 2 (Nrf2), and neurotrophic factors. All animals were ovariectomized 14 days before ischemic injury. Ischemic injury was induced for 1 h by middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion. Three days before MCAO, the vehicle-treated and the HBA-treated groups received intramuscular sesame oil and HBA (25 mg/kg BW), respectively. 2,3,5 Triphenyltetrazolium chloride (TTC) staining showed decreased infarct volume in the ischemic lesion of HBA-treated animals. HBA pretreatment also promoted functional recovery, as measured by the modified neurological severity score (mNSS; p < 0.05). Moreover, expression of PDI, Nrf2, BDNF, GDNF, and MBP genes increased by HBA treatment. In vitro, H2O2-induced PC12 cell death was prevented by 24 h HBA treatment, but bacitracin, a PDI inhibitor, attenuated this cytoprotective effect in a dose-dependent manner. HBA treatment for 2 h also induced nuclear translocation of Nrf2, possibly activating the intracellular antioxidative system. These results suggest that HBA protects against brain damage by modulating cytoprotective genes, such as Nrf2 and PDI, and neurotrophic factors.

Keywords ischemia, neuroprotection, neurotrophic factor, Nrf2, p-hydroxybenzyl alcohol (HBA), protein disulphide isomerase

Article

Research Article

Mol. Cells 2011; 31(3): 209-215

Published online March 31, 2011 https://doi.org/10.1007/s10059-011-0028-4

Copyright © The Korean Society for Molecular and Cellular Biology.

p-Hydroxybenzyl Alcohol Prevents Brain Injury and Behavioral Impairment by Activating Nrf2, PDI, and Neurotrophic Factor Genes in a Rat Model of Brain Ischemia

Kyung-Yoon Kam1,2,3, Seong Jin Yu4, Nahee Jeong4, Jeong Hwa Hong5, Angela M. A. Anthony Jalin4, Sungja Lee1, Yong Won Choi1, Chae Kwan Lee6, and Sung Goo Kang2,4,*

1Department of Occupational Therapy, Inje University, Gimhae 621-749, Korea, 2FIRST Research Group, Inje University, Gimhae 621-749, Korea, 3Institute of Aged Life Redesign, Inje University, Gimhae 621-749, Korea, 4School of Biological Sciences, Inje University, Gimhae 621-749, Korea, 5School of Food and Life Science , Inje University, Gimhae 621-749, Korea, 6Institute of Environmental and Occupational Medicine, Department of Occupational and Environmental Medicine, Busan Paik Hospital, Inje University, Busan 614-735, Korea

Correspondence to:*Correspondence: biosgkan@inje.ac.kr

Received: May 3, 2010; Revised: November 30, 2010; Accepted: December 8, 2010

Abstract

The therapeutic goal in treating cerebral ischemia is to reduce the extent of brain injury and thus minimize neurological impairment. We examined the effects of p-hydro-xybenzyl alcohol (HBA), an active component of Gastrodia elata Blume, on transient focal cerebral ische-mia-induced brain injury with respect to the involvement of protein disulphide isomerase (PDI), nuclear factor-E2-related factor 2 (Nrf2), and neurotrophic factors. All animals were ovariectomized 14 days before ischemic injury. Ischemic injury was induced for 1 h by middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion. Three days before MCAO, the vehicle-treated and the HBA-treated groups received intramuscular sesame oil and HBA (25 mg/kg BW), respectively. 2,3,5 Triphenyltetrazolium chloride (TTC) staining showed decreased infarct volume in the ischemic lesion of HBA-treated animals. HBA pretreatment also promoted functional recovery, as measured by the modified neurological severity score (mNSS; p < 0.05). Moreover, expression of PDI, Nrf2, BDNF, GDNF, and MBP genes increased by HBA treatment. In vitro, H2O2-induced PC12 cell death was prevented by 24 h HBA treatment, but bacitracin, a PDI inhibitor, attenuated this cytoprotective effect in a dose-dependent manner. HBA treatment for 2 h also induced nuclear translocation of Nrf2, possibly activating the intracellular antioxidative system. These results suggest that HBA protects against brain damage by modulating cytoprotective genes, such as Nrf2 and PDI, and neurotrophic factors.

Keywords: ischemia, neuroprotection, neurotrophic factor, Nrf2, p-hydroxybenzyl alcohol (HBA), protein disulphide isomerase

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

Share this article on

  • line
  • mail

Related articles in Mol. Cells

Molecules and Cells

eISSN 0219-1032
qr-code Download