Creatine kinase in non-muscle tissues and cells

Abstract

Over the past years, a concept for creatine kinase function, the 'PCr-circuit' model, has evolved. Based on this concept, multiple functions for the CK/PCr-system have been proposed, such as an energy buffering function, regulatory functions, as well as an energy transport function, mostly based on studies with muscle. While the temporal energy buffering and metabolic regulatory roles of CK are widely accepted, the spatial buffering or energy transport function, that is, the shuttling of PCr and Cr between sites of energy utilization and energy demand, is still being debated. There is, however, much circumstantial evidence, that supports the latter role of CK including the distinct, isoenzyme-specific subcellular localization of CK isoenzymes, the isolation and characterization of functionally coupled in vitro microcompartments of CK with a variety of cellular ATPases, and the observed functional coupling of mitochondrial oxidative phosphorylation with mitochondrial CK. New insight concerning the functions of the CK/PCr-system has been gained from recent M-CK null-mutant transgenic mice and by the investigation of CK localization and function in certain highly specialized non-muscle tissues and cells, such as electrocytes, retina photoreceptor cells, brain cells, kidney, salt glands, myometrium, placenta, pancreas, thymus, thyroid, intestinal brush-border epithelial cells, endothelial cells, cartilage and bone cells, macrophages, blood platelets, tumor and cancer cells. Studies with electric organ, including in vivo 31p_ NMR, clearly reveal the buffer function of the CK/PCr-system in electrocytes and additionally corroborate a direct functional coupling of membrane-bound CK to the Na+/K+-ATPase. On the other hand, experiments with live sperm and recent in vivo 31p-NMR measurements on brain provide convincing evidence for the transport function of the CK/PCr-system. We report on new findings concerning the isoenzyme-specific cellular localization and subcellular compartmentation of CK isoenzymes in photoreceptor cells, in glial and neuronal cells of the cerebellum and in spermatozoa. Finally, the regulation of CK expression by hormones is discussed, and new developments concerning a connection of CK with malignancy and cancer are illuminated. Most interesting in this respect is the observed upregulation of CK expression by adenoviral oncogenes. (Mol Cell Biochem 133/134: 193-220,1994) Key words: creatine kinase, functional coupling with cellular ATPases, spermatozoa, electrocytes, retina, cerebellum Abbreviations: M-CK, B-CK and Mi-CK refer to muscle-type, brain-type and mitochondrial-type creatine kinase, respectively, with the cytosolic isoforms MM-, MB-and BB-CK forming dimers and Mi-CK forming dimers as well as octamers; BGC -Bergmann

Protective effects of oral creatine supplementation on spinal cord injury in rats

“…34 ± 36 Creatine may decrease the e ects of trauma-induced hypoxia especially by bu ering intracellular ATP. 15,37 Due to improved cellular energetics, the cells are likely to be more resistant against calcium overload and noxious acidic pH values. 37 Additionally, neurons can be protected by creatine by inhibition of mitochondrial permeability transition pore opening via the stabilizing action of mitochondrial CK octamers.…”

“…15,37 Due to improved cellular energetics, the cells are likely to be more resistant against calcium overload and noxious acidic pH values. 37 Additionally, neurons can be protected by creatine by inhibition of mitochondrial permeability transition pore opening via the stabilizing action of mitochondrial CK octamers. 38 Furthermore, creatine's neuroprotective activity may also be related to its in¯uence on the synthesis and release of neurotransmitters.…”

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

“…The finding of increased carbonyl levels and decreased activity of CK further determines which crucial enzymes are finely involved in energetic impairments in this disorder. The CK system, consisting of a cytosolic and a mitochondrial isoform (MtCK) together with their substrates creatine and phosphocreatine, is one of the most important immediate energy buffering and transport systems of the cell, especially in muscle and neuronal tissue (394). CKs are prime targets of oxidative damage (74), leading to inactivation of both isoforms.…”

Cellular distributions of creatine kinase in branchia of euryhaline tilapia (Oreochromis mossambicus)

“…Accordingly, in vivo studies have suggested a direct coupling of CKATPase (2). An increase in CKB activity and brain energy metabolism constitutes a mechanism for coupling energy production (ATP) and energy storage (creatine phosphate) to meet rapidly increasing cellular energy demands (35). Muscle-type CK is functionally coupled to Na ϩ -K ϩ -ATPase activity, providing ATP for the ATPase reaction (27,28).…”

“…Three cytosolic CK isozymes [BB-CK (brain), MM-CK (muscle), and MB-CK (heart, lungs, stomach) (5, 8)] and two mitochondrial forms [sarcomeric MiCK (expressed mainly in heart and skeletal muscle and probably in some brain cells such as Purkinje neurons) and ubiquitous MiCK (expressed in many tissues)] are kinetically very similar but differ in their capacity to associate with subcellular organelles or protein structures (35,41). Three types (brain, muscle, and mitochondria) of CK have been demonstrated to exist in teleosts (4,26).…”