Biomaterial Database

Pyruvate kinase M2 isoform deletion in cone photoreceptors results in age-related cone degeneration. 2018

Ammaji Rajala, and Yuhong Wang, and Krutik Soni, and Raju V S Rajala

Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

The tumor form of pyruvate kinase M2 has been suggested to promote cellular anabolism by redirecting the metabolism to cause accumulation of glycolytic intermediates and increasing flux through the pentose phosphate pathway, which is a metabolic pathway parallel to glycolysis. Both rod and cone photoreceptors express the tumor form of pyruvate kinase M2. Recent studies from our laboratory show that PKM2 is functionally important for rod photoreceptor structure, function, and viability. However, the functional role of PKM2 in cones is not known. In this study, we conditionally deleted PKM2 in cones (cone-cre PKM2-KO) and found that loss of PKM2 results in the upregulation of PKM1 and a significant loss of cone function and cone degeneration in an age-dependent manner. Gene expression studies on cone-cre PKM2-KO show decreased expression of genes regulating glycolysis, PPP shunt, and fatty acid biosynthesis. Consistent with these observations, cones lacking PKM2 have significantly shorter cone outer segments than cones with PKM2. Our studies clearly suggest that PKM2 is essential for the anabolic process in cones to keep them alive for normal functioning and to support cone structure.

UI	MeSH Term	Description	Entries
D011770	Pyruvate Kinase	ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC 2.7.1.40.	L-Type Pyruvate Kinase,M-Type Pyruvate Kinase,M1-Type Pyruvate Kinase,M2-Type Pyruvate Kinase,Pyruvate Kinase L,R-Type Pyruvate Kinase,L Type Pyruvate Kinase,M Type Pyruvate Kinase,M1 Type Pyruvate Kinase,M2 Type Pyruvate Kinase,Pyruvate Kinase, L-Type,Pyruvate Kinase, M-Type,Pyruvate Kinase, M1-Type,Pyruvate Kinase, M2-Type,Pyruvate Kinase, R-Type,R Type Pyruvate Kinase
D012160	Retina	The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent.	Ora Serrata
D004596	Electroretinography	Recording of electric potentials in the retina after stimulation by light.	Electroretinographies
D006019	Glycolysis	A metabolic process that converts GLUCOSE into two molecules of PYRUVIC ACID through a series of enzymatic reactions. Energy generated by this process is conserved in two molecules of ATP. Glycolysis is the universal catabolic pathway for glucose, free glucose, or glucose derived from complex CARBOHYDRATES, such as GLYCOGEN and STARCH.	Embden-Meyerhof Pathway,Embden-Meyerhof-Parnas Pathway,Embden Meyerhof Parnas Pathway,Embden Meyerhof Pathway,Embden-Meyerhof Pathways,Pathway, Embden-Meyerhof,Pathway, Embden-Meyerhof-Parnas,Pathways, Embden-Meyerhof
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015151	Immunoblotting	Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.	Dot Immunoblotting,Electroimmunoblotting,Immunoelectroblotting,Reverse Immunoblotting,Immunoblotting, Dot,Immunoblotting, Reverse,Dot Immunoblottings,Electroimmunoblottings,Immunoblottings,Immunoblottings, Dot,Immunoblottings, Reverse,Immunoelectroblottings,Reverse Immunoblottings
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D017949	Retinal Cone Photoreceptor Cells	Photosensitive afferent neurons located primarily within the FOVEA CENTRALIS of the MACULA LUTEA. There are three major types of cone cells (red, blue, and green) whose photopigments have different spectral sensitivity curves. Retinal cone cells operate in daylight vision (at photopic intensities) providing color recognition and central visual acuity.	Cone Photoreceptors,Cones (Retina),Cone Photoreceptor Cells,Photoreceptors, Cone,Retinal Cone,Retinal Cone Cells,Retinal Cone Photoreceptors,Cell, Cone Photoreceptor,Cell, Retinal Cone,Cells, Cone Photoreceptor,Cells, Retinal Cone,Cone (Retina),Cone Cell, Retinal,Cone Cells, Retinal,Cone Photoreceptor,Cone Photoreceptor Cell,Cone Photoreceptor, Retinal,Cone Photoreceptors, Retinal,Cone, Retinal,Cones, Retinal,Photoreceptor Cell, Cone,Photoreceptor Cells, Cone,Photoreceptor, Cone,Photoreceptor, Retinal Cone,Photoreceptors, Retinal Cone,Retinal Cone Cell,Retinal Cone Photoreceptor,Retinal Cones
D018345	Mice, Knockout	Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.	Knockout Mice,Mice, Knock-out,Mouse, Knockout,Knock-out Mice,Knockout Mouse,Mice, Knock out
D020033	Protein Isoforms	Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.	Isoform,Isoforms,Protein Isoform,Protein Splice Variant,Splice Variants, Protein,Protein Splice Variants,Isoform, Protein,Isoforms, Protein,Splice Variant, Protein,Variant, Protein Splice,Variants, Protein Splice