ABSTRACT
Traumatic brain injury (TBI) is a major reason for temporary or permanent dyskinesia and cognitive impairment of the organism. Generally, TBI induces subsequent neuroinflammation to assist cell debris removal and tissue repair and regeneration after injury. However, overactivation or long-term activation of immune cells will exacerbate nerve damage or death, cause cognitive dysfunction, and ultimately lead to neurodegenerative diseases. Therefore, secondary damage caused by persistent inflammation is a key component of TBI pathological process. As the main metabolite of anaerobic glycolysis, lactate is increased after TBI and participates in brain inflammation as an important immune regulatory molecule rather than a metabolic waste. Importantly, histone lysine lactylation as a novel type of histone post-translational modifications (HPTM) derived from lactate allows lactate to participate in the regulation of complex immunopathophysiological processes of the central nervous system after TBI. Further study on the process of histone lactylation and its immune regulation mechanism during TBI may provide new insights for early intervention and improvement of TBI prognosis. Thus, the authors reviewed the role of histone lactylation in the immune regulation of TBI, so as to further elucidate the mechanism of TBI and the explore new warning and prevention measures from the perspective of HPTM.
ABSTRACT
Hypoxia inducible factor(HIF)is a key factor in the regulation of oxygen homeostasis, and its expression level is mainly influenced by oxygen concentration in the adaptation of the body to chronic hypoxia, with which many pediatric diseases are closely associated.The response to hypoxia can be altered by HIF and its mediated downstream signaling pathways, in addition to epigenetic modifications such as regulation of overall methylation or histone modification levels to adapt to hypoxic environments.Previous studies have shown that the transcriptional activity and stability of HIF are interrelated with various histone modifications including methylation/demethylation, hydroxylation, deacetylation, phosphorylation, and lactylation, which makes the study of epigenetic modification correlation deserves to be explored in depth as an important potential target for regulating HIF expression levels.