br Introduction Hexokinase HK is an enzyme that catalyses

Introduction Hexokinase (HK) is an enzyme that catalyses the transfer of phosphate from ATP to glucose in the first step of glucose metabolism (Wilson, 1995, Wilson, 2003). In mammalian, HK has four important isozymes which are designated as HK1, HK2, HK3 and HK4 (Wilson, 1995, Wilson, 2003). HK1 is considered to be “brain HK”, it is the predominant HK form in the brain. However, it is ubiquitously expressed in all mammalian tissues, and most physiological, hormonal and metabolic factors have no effect on its expression (Calmettes et al., 2015, Purich and Fromm, 1971). HK2 is also called “muscle HK”, it is primarily expressed in insulin-sensitive tissues, such as skeletal muscle, heart and adipose tissues (Calmettes et al., 2015, Mandarino et al., 1995, Nederlof et al., 2014). HK3 is ubiquitously expressed in most tissues at relatively low level; however, its higher abundance levels have been reported in lung, liver and kidney (Lowes et al., 1998, Okatsu et al., 2012, Wyatt et al., 2010). In myeloid cells, particularly granulocytes, HK3 is the predominant hexokinase. (Federzoni et al., 2014). HK4, is also known as glucokinase, mainly exists in the liver and pancreas. In terms of kinetics and function, it is different from the other three HKs. HK4 has a lower affinity for glucose than the other three HKs (Cardenas et al., 1998). The function and tissue specific distribution of the HK isoforms are affected by the organism's pathophysiological state. For example, the expression and activity of some isoforms are increased in tumor tissue, this makes the tumor tissue can still get enough energy under hypoxia, and many intermediates of glycolysis can be used by tumor 8-pCPT-2-O-Me-cAMP-AM to synthesize proteins, nucleic acids and lipids, thus providing the necessary material basis for the growth and proliferation of tumor cells (Cho et al., 2015, Gao and Chen, 2015). Some isoforms are also been reported relating to injury, inflammation, apoptosis and cell survival (Clemons and Toledo-Pereyra, 2015, Wyatt et al., 2010). Spinal cord injury (SCI) is the injury of spinal cord resulting in devastating loss of motor and sensory functions (Gwak et al., 2016). SCI also includes inflammation, apoptosis and other pathophysiological processes (Cox et al., 2015). However, the changes in expression and function of these isoforms have not been reported in the injured spinal cords so far. Recently, using RNA-Sequencing, we found that HK3 was significantly upregulated at mRNA level in the injured spinal cords at subacute stage (Shi et al., 2017). This is an interesting phenomenon. HK3 lacks hydrophobic N-terminal sequences which are known being used to bind mitochondria by HK1 and HK2 (Wyatt et al., 2010). Using Novikoff rat hepatoma cell line and HK3-overexpressed HEK293 cells, Wyatt et al. reported that HK3 could exert cytoprotective effects against oxidative stress by increasing ATP levels, reducing oxidant-induced ROS, preserving mitochondrial membrane potential and increasing mitochondrial biogenesis (Wyatt et al., 2010). However, its expression, cellular localization and function in the lesion microenvironment after SCI are still unclear.
Materials and methods
Results
Discussion There are two pathological processes in traumatic SCI: primary injury and secondary injury. Primary injury is the immediate damages of various spinal cord components caused by mechanical damage. Secondary injury is triggered by the primary injury which affects multiple biological processes and produces extensive temporal changes at molecular and cellular levels (Liu et al., 2009). Primary injury can directly cause neuronal necrosis. In secondary injury phase, in addition to important cellular events (activation of microglia and astrocytes, infiltration of leukocytes, oligodendrocyte cell death, axon demyelination, neuronal defects, etc.), some metabolism-related molecular events also play an important role in the pathological process of SCI (Anwar et al., 2016).