Abstract
ATG5-induced autophagy is triggered in the early stages after SAH, which plays a vital role in subarachnoid hemorrhage (SAH). Acyl-CoA synthetase short-chain family 2 (ACSS2) is not just involved in energy metabolism but also binds to TEFB to form a complex translocated to related autophagy genes to regulate the expression of autophagy-related genes. However, the contribution of ACSS2 to the activation of autophagy in early brain injury (EBI) after SAH has barely been discussed. The purpose of this study was to investigate the alterations of ACSS2 and its neuroprotective effects following SAH. We first evaluated the expression of ACSS2 at different time points (6, 12, 24, and 72 h after SAH) in vivo and primary cortical neurons stimulated by oxyhemoglobin (OxyHb). Subsequently, adeno-associated virus and lentivirus were used to regulate ACSS2 expression to investigate the effect of ACSS2 after SAH. The results showed that the ACSS2 level decreased significantly in the early stages of SAH and was minimized at 24 h post-SAH. After artificial intervention to overexpress ACSS2, ATG5-induced autophagy was further enhanced in EBI after SAH, and neuronal apoptosis was alleviated to protect brain injury. In addition, brain edema and neurological function scores were improved. These results suggest that ACSS2 plays an important role in the neuroprotection against EBI after SAH by increasing ATG5-induce autophagy and inhibiting apoptosis.
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Abbreviations
- ACSS2:
-
Acyl-CoA synthetase short-chain family 2
- ATG5:
-
Autophagy protein 5
- SAH:
-
Subarachnoid hemorrhage
- EBI:
-
Early brain injury
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Funding
This work was grant-supported by the Jiangsu Natural Science Foundation of China (Grant No. SBK2019022915), the National Natural Science Foundation of China (Grant No. 82071328), Jiangsu Medical Priority Talent Project of China (Grant No. ZDRCA2016094) and Jiangsu Health Commission Scientific Research Key Project of China (Grant No. K2019017).
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WH, XZ: Conceptualizations and methodology. WH, LZ, RZ: Investigation. WH, QW, ZZ: Data analysis. WH, CD: Writing—original draft. XZ, XZ: Writing—review & editing. XZ: Resources. All authors of this article have given their permission to publish the article.
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He, W., Zhou, X., Wu, Q. et al. Acetyl CoA synthase 2 potentiates ATG5-induced autophagy against neuronal apoptosis after subarachnoid hemorrhage. J Mol Histol 53, 511–521 (2022). https://doi.org/10.1007/s10735-022-10057-x
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DOI: https://doi.org/10.1007/s10735-022-10057-x