The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury
Open accessAbstract
Summary Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (KO), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity. Furthermore, downregulation of hexosamine biosynthetic pathway in KO hearts decreased protein O-linked-N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH resulting in significant decreases in glucose oxidation. Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury. Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome. These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.
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Self-citationAnalysis of mitochondrial function in situ in permeabilized muscle fibers, tissues and cells
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Cited by
Cardiac Energy Metabolism in Heart Failure
Lopaschuk, G. D., Karwi, Q. G., Tian, R., Wende, A. R., & Abel, E. D. (2021) · Circulation Research · doi:10.1161/circresaha.121.318241 · Cited by 1,373
Self-citationComprehensive quantification of fuel use by the failing and nonfailing human heart
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Metabolism of Amino Acids in Cancer
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Targeting Mitochondria-Inflammation Circuit by β-Hydroxybutyrate Mitigates HFpEF
Deng, Y., Xie, M., Li, Q., Xu, X., Ou, W., Zhang, Y., Xiao, H., Yu, H., Zheng, Y., Liang, Y., et al. (2021) · Circulation Research · doi:10.1161/circresaha.120.317933 · Cited by 409
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Metadata
- Authors
- Li, T., Zhang, Z., Kolwicz, S. C., Abell, L., Roe, N. D., Kim, M., Zhou, B., Cao, Y., Ritterhoff, J., Gu, H., Raftery, D., Sun, H., & Tian, R.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 25
- Issue
- 2
- Pages
- 374-385
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2587537033
- Cited by
- 401
- References
- 40
- FWCI
- 19.47
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Li, T., Zhang, Z., Kolwicz, S. C., Abell, L., Roe, N. D., Kim, M., Zhou, B., Cao, Y., Ritterhoff, J., Gu, H., Raftery, D., Sun, H., & Tian, R. (2017). Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury. Cell Metabolism. https://doi.org/10.1016/j.cmet.2016.11.005
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