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    • In skeletal as well as in the heart muscle the

    2022-09-15

    In skeletal as well as in the XCT790 muscle, the same FBPase isozyme is present (Gizak and Dzugaj, 2003). On the other hand, different isoforms of 6-fructo-2 kinase/fructose-2,6-bisphosphatase (FBPase-2/PFK-2) have been discovered in muscle fibres and cardiomyocytes (Okar et al., 2001, Marsin et al., 2000). In skeletal muscle, two isoforms of this enzyme have been found: predominantly the muscle isozyme and a small amount of the liver isozyme, both of which are encoded by the same gene, but as a result of post-translational splicing the muscle isoform is devoid of the domain containing Ser 32 and is not regulated by phosphorylation (Okar et al., 2001). The heart FBPase-2/PFK-2 is encoded by a different gene and is also controlled by phosphorylation but, contrary to the liver FBPase-2/PFK-2, the heart isoenzyme is phosphorylated at the C-terminus by several protein kinases, which results in PFK-2 activation (Marsin et al., 2000). Therefore, a different mechanism of carbohydrate metabolism could be expected in the heart muscle, in comparison with the skeletal muscle. Intercalated discs are the specific contact sites between neighboring cardiomyocytes necessary to ensure proper work of a heart. Our results have shown that FBPase and aldolase colocalised also on the intercalated discs. They probably create an additional glyconeogenic compartment and presume this colocalisation is important for the intercalated disc function. At this compartment aldolase and FBPase could associate with α-actinin which is also the protein of intercalated disc (Imanaka-Yoshida et al., 1993, Pashmforoush et al., 2001). On the other hand, α-actinin-FBPase complex is very sensitive to calcium ions (Mamczur et al., 2005). The increase of the Ca2+ concentration resulted in the dissociation of the FBPase from the Z-line but not form the intercalated disc (Gizak et al., 2004). It rather suggests that FBPase, and perhaps aldolase, are not associated with the intercalated disc via the interaction with the α-actinin. Another possibility is that the α-actinin–FBPase complex on the intercalated disc is stabilised by an unknown protein. In the present paper we have shown that aldolase, as well as FBPase, colocalised in the heterochromatin region of the cardiomyocyte nuclei. It is not clear if FBPase and aldolase create a complex in the heterochromatin region. However, a comparison of the concentrations of both enzymes within the nuclei suggests the possibility of complex formation. In the pig cardiomyocyte nuclei (with the nucleus volume of ca. 307μm3), the FBPase concentration is 0.6μM (Gizak and Dzugaj, 2003), and it is the same as the aldolase concentration: 0.6μM (Mamczur and Dzugaj, 2004). Therefore, it is possible that the nuclear aldolase and FBPase could be involved in the production of fructose 6-phosphate within the nuclei. On the other hand, the restriction of their colocalisation to the heterochromatin region suggests their involvement in the processes specific to the nucleus. Several enzymes of carbohydrate metabolism are involved in the nuclei in processes highly distinct from their function in the cytoplasm. Glyceraldehyde 3-phosphate dehydrogenase is involved in the transcription (Sirover, 1997), phosphoglycerate kinase may participate in DNA synthesis as well as cell-cycle progression (Popanda et al., 1998) and lactate dehydrogenase participates in DNA reparation (Ronai, 1993). Summarising, the function of FBPase and aldolase in the nucleus is still not fully known and needs to be investigated further. Another question concerns the transport of proteins from the cytoplasm to the nucleus. To examine the dependence of one enzyme on the translocation of the other, we have performed the translocation of FBPase and aldolase, modified by FITC and TRITC, respectively, into the isolated nuclei of cardiomyocytes. Our results revealed that aldolase and FBPase are translocated into the nuclei independently. The control reaction (with lectin WGA) has confirmed that both enzymes are translocated through the nuclear pore complexes. The possibility of the transport through the nuclear pore complexes of FBPase via its potential NLS group was previously discussed (Gizak and Dzugaj, 2003). The mode of translocation of aldolase to the nucleus is unknown. The NLS has not been found in muscle aldolase primary structure. However, presence of NLS is not necessary to enable the transport of proteins into a nucleus. Although the hepatic glucokinase does not contain NLS, it is transported to the nuclei via interaction with the regulatory protein (GKRP) (Toyoda et al., 1995, Shiota et al., 1999, Payne et al., 2005). Similarly, aldolase could be translocated to the nuclei through an interaction with a protein, so far unknown.