Staving off Mitochondrial
DNA Depletion with Nucleoside Import♦
♦ See referenced article, J. Biol. Chem. 2013, 288, 5072–5079
Thymidine kinase 2 (TK2) is a salvage enzyme tasked with delivering a constant supply of deoxythymidine triphosphate (dTTP) to the mitochondria to maintain a balanced deoxyribonucleoside triphosphate (dNTP) pool and to support mitochondrial DNA replication and integrity. A deficiency in TK2 causes depletion of mtDNA, resulting in a number of devastating diseases. In this Paper of the Week, a team led by Anna Karlsson at the Karolinska Institute in Sweden reported a potential strategy for reversing the symptoms of TK2 deficiency in transgenic mice. The team expressed the nucleoside kinase from Drosophila melanogaster (Dm-dNK) in the cell nucleus of TK2-deficient mice, which compensated for the loss of mitochondrial deoxythymidine monophosphate (dTMP) synthesis in differentiated tissue. Ultimately, the mice displayed normal growth, behavior, and levels of mtDNA, opening the door to new potential therapies for TK2 deficiency.
doi: 10.1074/jbc.P112.437152 February 15, 2013 The Journal of Biological Chemistry, 288, 5080.
Introduction to the Thematic Minireview Series “Molecular bases of disease: Asthma”
Search for the word “asthma” in the Journal of Biological Chemistry’s archives, and more than 900 matches will come up. That’s a testament to the role that JBC authors have played and today are playing in the pursuit of a better understanding of the molecular roots of the illness and, ultimately, improved therapies for asthma sufferers.
Asthma is said to have been first identified and named by Hippocrates around 450 B.C., but for centuries it went misunderstood and in some cases was even attributed to psychological and emotional instability. While most people today are familiar with the trademark symptoms of asthma — wheezing, coughing, breathlessness, chest tightness — from chronically inflamed airways and passageway spasms, the reality, according to the Centers for Disease Control and Prevention, is that “in most cases, we don’t know what causes asthma, and we don’t know how to cure it.”
First Published on July 28, 2011, doi: 10.1074/jbc.R111.287284 jbc.R111.287284.
Flower Power: The Story of a Flavone and Bone♦
♦ See referenced article, J. Biol. Chem. 2011, 286, 27882–27893
Flavonoids, or plant pigments, are among the most popular natural compounds packaged as nutritional supplements for consumers seeking to improve cognition or ward off various other ailments (case in point: ginkgetin, derived from the leaves of the Ginkgo biloba tree). Naturally, certain flavonoids alleged to possess estrogen-like activities that promote bone renewal have piqued the interest of osteoporosis researchers. In their JBC Paper of the Week, Tsim and co-workers evaluated 36 flavonoids for their ability to promote osteoblast differentiation, as indicated by alkaline phosphatase activity, as well as osteogenesis in vitro. Using cultured osteoblasts from the skulls of newborn rats, the team concluded that the flavone baicalin, which is derived primarily from the root of the purple flowering plant Scutellaria baicalensis (Baikal Skullcap) and which has been used for centuries by traditional Chinese medicine practitioners, is the best inducer of alkaline phosphatase (ALP). Significantly, the authors report that the osteogenic effect of baicalin is not mediated through estrogen receptors. Rather, the authors argue that the baicalin-induced effect is mediated by the Wnt/β-catenin signaling pathway.
doi: 10.1074/jbc.P111.236281 August 12, 2011 The Journal of Biological Chemistry, 286, e99961.
Chicken Retina Gobbles Up Oxygen Served by Globin E♦
♦ See referenced article, J. Biol. Chem. 2011, 286, 26507–26515
The vertebrate retina consumes large amounts of oxygen, but getting oxygen to the avian retina is no walk in the park. Birds have high metabolic rates, large eyes, and thick retinae that largely lack deep or superficial capillaries. Instead, oxygen must be delivered to the retina through the choroidal vascular bed and the pecten oculi, a comb-like structure of blood vessels that stretches from the retina into the vitreous chamber of the eye. In this Paper of the Week, Thorsten Burmester and colleagues take a closer look at an oxygen-binding hemeprotein that appears to be expressed only in the eyes of birds: globin E (or GbE). The team characterized chicken GbE, found in large quantities in photoreceptor cells, through comparative genomics, molecular and histological characterization of expression patterns, and biochemical analyses of recombinant GbE. The results showed that in retinal tissues GbE acts much like myoglobin does in the myocytes of the heart and skeletal muscles, storing oxygen and facilitating its diffusion. The authors say this doesn’t definitely exclude other duties for GbE, “such as protection from reactive oxygen species or a redox reaction which may be induced by light in the outer segments of the photoreceptor cells.” Lacking an antibody that recognizes the chicken neuroglobin (Ngb), the team could not determine that hemeprotein’s concentration; however, it did find that Ngb mRNA levels were 100-fold lower than those of GbE, suggesting that Ngb does not play a major role in oxygen supply in the chicken eye but likely has a different, yet to be determined, function.
doi: 10.1074/jbc.P111.224634 July 29, 2011 The Journal of Biological Chemistry, 286, e99958.