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Stanniocalcin-1 Protected Astrocytes from Hypoxic Damage Through the AMPK Pathway

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Abstract

Our previous studies revealed that the expression of stanniocalcin-1 (STC1) in astrocytes increased under hypoxic conditions. However, the role of STC1 in hypoxic astrocytes is not well understood. In this work, we first showed the increased expression of STC1 in astrocyte cell line and astrocytes in the brain tissues of mice after exposure to hypoxia. Then, we found that knockdown of STC1 inhibited cell viability and increased apoptosis. These effects were mediated by decreasing the levels of SIRT3, UCP2, and glycolytic genes and increasing the levels of ROS. Further studies suggested that STC1 silencing promoted oxidative stress and suppressed glycolysis by downregulating AMPKα1. Moreover, HIF-1α knockdown in hypoxic astrocytes led to decreased expression of STC1 and AMPKα1, indicating that the expression of STC1 was regulated by HIF-1α. In conclusion, our study showed that HIF-1α-induced STC1 could protect astrocytes from hypoxic damage by regulating glycolysis and redox homeostasis in an AMPKα1-dependent manner.

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Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Abbreviations

ALDOA:

Aldolase A

AMPK:

AMP-Activated Protein Kinase

ERK:

Extracellular Signal-Regulated Protein Kinases

GDNF:

Glial Cell Line-Derived Neurotrophic Factor

GLUT1:

Glucose Transporter 1

HIF-1α:

Hypoxia Inducible Factor-1α

IHC:

Immunohistochemical (IHC)

LDHA:

Lactate Dehydrogenase A

NRF2:

Nuclear Factor E2-Related Factor 2

PGK1:

Phosphoglycerate Kinase 1

ROS:

Reactive Oxygen Species

SIRT3:

Sirtuin 3

STC1:

Stanniocalcin-1

UCP2:

Uncoupling Protein 2

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Acknowledgements

This research was supported by grants from Army Medical University (Grant No. 2017XQN05), Youth Cultivation Project of PLA (Grant No. 19QNP002) and the program of Chongqing Talents.

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Authors and Affiliations

  1. Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Chongqing, China

    Binda Sun, Shu He, Bao Liu, Gang Xu,  Guoji E, Lan Feng, Licong Xu, Wenqi Zhao, Jian Chen, Yuqi Gao & Erlong Zhang

  2. Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Chongqing, China

    Binda Sun, Shu He, Bao Liu, Gang Xu,  Guoji E, Lan Feng, Licong Xu, Dewei Chen, Wenqi Zhao, Jian Chen, Yuqi Gao & Erlong Zhang

  3. Key Laboratory of High Altitude Medicine, People’s Liberation Army, Chongqing, China

    Binda Sun, Shu He, Bao Liu, Gang Xu,  Guoji E, Lan Feng, Licong Xu, Dewei Chen, Wenqi Zhao, Jian Chen, Yuqi Gao & Erlong Zhang

  4. Department of Pathophysiology, College of High Altitude Military Medicine, Army Medical University, Chongqing, China

    Dewei Chen

  5. Number 30, Gaotanyan Street, District of Shapingba, Chongqing, 400038, China

    Yuqi Gao & Erlong Zhang

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  1. Binda Sun
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  2. Shu He
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Contributions

BS performed experiments, interpreted the data, and wrote the manuscript. SH, BL, GX, GE, LF, LX and WZ participated experiments. DC and JC participated in data analysis and manuscript writing. EZ and YG conceived the study design, experimental plan, and manuscript writing. All authors discussed the results and critically reviewed the manuscript.

Corresponding authors

Correspondence to Yuqi Gao or Erlong Zhang.

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Supplementary Information

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Figure S1. The expression of GFAP in HEB cells. Green: GFAP; Purple: Nucleoli. Supplementary material 1 (TIF 1072.4 kb)

11064_2021_3393_MOESM2_ESM.tif

Figure S2. STC1 expression in immunohistochemcal analysis of mouse brain tissues. Supplementary material 2 (TIF 10995.7 kb)

11064_2021_3393_MOESM3_ESM.tif

Figure S3. 1 The TUNEL assay in mouse brain tissues under normoxic and 5,800-m hypobaric hypoxic conditions for 1, 3 and 7 days (n=6). Blue: DAPI; Green: GFAP; Red: TUNEL. Supplementary material 3 (TIF 9787.2 kb)

Supplementary material 4 (DOCX 17.4 kb)

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Sun, B., He, S., Liu, B. et al. Stanniocalcin-1 Protected Astrocytes from Hypoxic Damage Through the AMPK Pathway. Neurochem Res 46, 2948–2957 (2021). https://doi.org/10.1007/s11064-021-03393-z

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  • DOI: https://doi.org/10.1007/s11064-021-03393-z

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