Nature, 456, 745-749, 2008
Gordon GR, Choi HB, Rungta RL, Ellis-Davies GC, & Macvicar BA
Brain metabolism dictates the polarity of astrocyte control over arterioles
This excellent work demonstrates a metabolic coupling of cerebral blood to the lactate/pyruvate ratio and the related NADH/NAD ratio. The authors tested the hypothesis that the metabolic
state of the tissue dictates the type of astrocyte influence on arteriole diameter. Neural activity of dendrites consumes oxygen and leads to a reduction in oxygen pressure, which occurs before
the increase in cerebral blood flow and stimulates glycolysis, causing increased lactate release. Lactate, being vasoactive, can dynamically alter microvasculature diameter in an oxygen-
dependent manner. Vasodilation thus occurs in the brain region experiencing low oxygen tension. Extracellular lactate reduces transporter-mediated uptake from the external space of PGE2.
Manipulating this metabolic circuit may represent a therapeutic strategy for treating the decline in cerebral blood flow associated with some dementias and after stroke. The authors were able
to reliably measure extracellular lactate levels using our L-Lactate Assay Kit (cat#: A-108S and A-108L). Please note that a D-Lactate Assay Kit has recently become available. Additional
citations of our L-Lactate Assay Kit are listed below.
J Pharmacol Exp Ther, 333:341-50, 2010
PLoS One, 5:e13820, 2010
Am J Physiol, 294:E148-E156, 2008
J Fish Biol, 72:1831-1840, 2008
J Biol Chem, 282:1607-14, 2007
J Bacteriol, 189:8079-87, 2007
J Biol Chem, 281:26769-26773, 2006
Proc Natl Acad Sci USA, 103, 18751-18756, 2006
Zaki M, Andrew N, & Insall RH
Entamoeba histolytica cell movement: A central role for self-generated chemokines and chemorepellents
This interesting work by Zaki et al sought to understand the mechanism governing motility of E. histolytica, the cause of amoebic dysentery, within the G.I. tract. It is estimated that ~50 million
people worldwide suffer the severe morbidity caused by E. histolytica, with ~100,000 deaths each year. The authors discovered that components of E. histolytica-conditioned culture medium
are key determinants of cell motility. Using an improved chemotaxis assay, they identified the key extracellular signals mediating Entamoeba chemotaxis. Medium conditioned by E. histolytica
caused both chemokinesis and negative chemotaxis. Random movement was accelerated in conditioned compared with fresh medium, and cells moved efficiently away from conditioned
medium by negative chemotaxis. Ethanol, the product of Entamoeba glucose metabolism, is the principal component of the chemokinetic response. Since the nonpathogenic Entamoeba dispar
does not show such behavior, this finding suggests that negative chemotaxis may play a key role in E. histolytica pathogenesis. Using our Ethanol Assay Kit (cat#: A-111), the authors were
able to confirm that the chemokinetic but not the chemotactic effect of conditioned medium could be completely recreated by physiological ethanol levels. Related assay kits offered by us
include Alcohol Dehydrogenase Assay Kit and Aldehyde Dehydrogenase Assay Kit. Additional citations of our Ethanol Assay kit are listed below.
Cereal Chemistry, 85:322-328, 2008
Alcoholism, 34:997-1005, 2010
J Biol Chem, 286:99-113, 2011
Giulivi C, Ross-Inta C, Omanska-Klusek A, Napoli E, Sakaguchi D, Barrientos G, Allen PD, & Pessah IN
Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice
Malignant hyperthermia (MH), a genetic disorder of skeletal muscle associated with mutations in the ryanodine receptor (RyR1), is characterized by an abnormal response to muscle
depolarizing muscle relaxants. This insightful study focused metabolic differences in MH susceptible and normal skeletal muscle under basal conditions using C57BL6 WT mice and C57BL6
knock-in mice expressing the R163CRyR1 mutation, which is one of the most common human MH mutations. They found that the R163C skeletal muscle exhibited a significant increase in
matrix Ca2+, increased ROS production, and lower expression of mitochondrial proteins. Using our Glyceraldehyde-3-Phosphate (GAPDH) Dehydrogenase Assay Kit (cat#: E-101), they
were able to demonstrate that these changes are associated with lower GAPDH expression and activity. Lower glucose utilization thus suggested a switch to an energy inefficient state
characterized by both low oxidative phosphorylation and glycolysis. Other glycolytic enzymes can be studied using our Hexokinase Assay Kit, Lactate Dehydrogenase Assay Kit, and Glucose
Assay Kit. Additional citations of our GAPDH Assay kit are listed below.
Gynecol Oncol, 107:450-457, 2007
Mol Cell Biochem, 321:45-52, 2009
J Orthopedic Res, 28:914-920, 2010
Cancer Res, 66:1684-1693, 2006
Dang DT, Chen F, Gardner LB, Cummins JM, Rago C, Bunz F, Kantsevoy SV, & Dang LH
Hypoxia-inducible factor-1α promotes nonhypoxia-mediated proliferation in colon cancer cells and xenografts
The hypoxia-inducible transcription factor HIF-1α is strongly associated with cancer cell growth and survival. Although HIF-1α expression is correlated with patient mortality, HIF-1α-deficient
tumors can paradoxically grow faster than their wild-type counterparts. In this article, the authors disrupted HIF-1α by targeted homologous recombination in HCT116 and RKO human colon
cancer cells, and elegantly show that HIF-1α promotes nonhypoxia-mediated cell proliferation in vitro and in vivo in a subset of colon cancers. Using our ATP Assay Kit (cat#: A-107), they
measured levels of ATP and other metabolites in glycolysis under normoxic culture conditions, and found that loss of HIF-1α induced significant decreases in intracellular ATP. An interesting
clinical implication from the work is that therapy targeting HIF-1α may be effective against tumors in which HIF-1α contributes to nonhypoxic cell proliferation. The authors also used our L-
Lactate Assay Kit and LDH Assay Kit. Additional citations of our ATP Assay Kit are listed below.
Mol Cancer, 9:293-304, 2010
J Ethnopharmacol, 130: 614-620, 2010
Phytotherapy Research, in press, 2011
Eur J Pharmacol, 627: 85-91, 2010
J Mol Cell Cardiol, 45:385-393, 2008
Chiu J, Farhangkhoee H, Xu BY, Chen S, George B, & Chakrabarti S
PARP mediates structural alterations in diabetic cardiomyopathy
Diabetic cardiomyopathy is a unique disease that directly affects the structure and the function of the myocardium in the absence of coronary artery disease or hypertension. Increased
oxidative stress from chronic hyperglycemia may have a causative role in the disease progression involving activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP). The
authors investigated the role of PARP in the development of structural changes in the diabetic heart, and determined whether these changes might be mediated by p300, a histone
acetyltransferase. Two models of diabetic complications were used to determine the role of PARP in oxidative stress and fibrosis in the heart. Using our Catalase Assay Kit (cat#: E-100), the
authors demonstrated that hyperglycemia caused upregulation of extracellular matrix proteins and p300 and increased oxidative stress. Specifically, the PARP−/− control mice had significantly
lower catalase activities compared to the WT controls. This study thus nicely illustrates a PARP- and p300-dependent mechanism contributing to the development of structural alterations in the
diabetic heart. Related assay kits offered by us include Peroxide Assay and Lipid Peroxidation Assay Kits. Additional citations of our Catalase Assay Kit are listed below.
PLoS One, 5:e12427, 2010
Cancer Res, 69: 5560-5567, 2009
Cancer Res, 69:5560-5567, 2009
Lynch J, Fukuda Y, Krishnamurthy P, Du G, & Schuetz JD
Cell survival under stress is enhanced by a mitochondrial ATP-binding cassette transporter that regulates hemoproteins
The ATP-binding cassette (ABC) transporter ABCB6 gene is amplified in camptothecin-resistant cells, and its overexpression is associated with multiagent resistance. The authors showed that
increased ABCB6 expression alters the levels of cellular hemoproteins and provides a cell survival advantage. Using our Lactate Dehydrogenase (LDH) Assay Kit (cat#: E-107) to
determine the activity of cytosolic LDH, they showed that increased heme in ABCB6-expressing cells did not alter the expression of either mitochondrial or cytosolic proteins. The ABCB6
overexpressor was not found to be resistant to cytotoxic challenge, but was resistant to cyanide and hydrogen peroxide stress. Thus, the effect of ABCB6 upregulation on multiple
hemoproteins may promote acquisition of multiagent resistance. This dominant effect of ABCB6 has implications for mitochondrial diseases related to defects in cytochrome c oxidase and for
other biochemical processes dependent on heme synthesis. Additional assay kits relevant in the study of glucose metabolism include Hexokinase Assay Kit, L-Lactate Assay Kit, D-Lactate
Assay Kit, G6PD Assay Kit, and Glucose Assay Kit. Additional citations of our LDH Assay kit are listed below.
Cancer Res, 66:1684-1693, 2006
J Anim Sci, 87:3124-3133, 2009
Gordon GR, Choi HB, Rungta RL, Ellis-Davies GC, & Macvicar BA
Brain metabolism dictates the polarity of astrocyte control over arterioles
This excellent work demonstrates a metabolic coupling of cerebral blood to the lactate/pyruvate ratio and the related NADH/NAD ratio. The authors tested the hypothesis that the metabolic
state of the tissue dictates the type of astrocyte influence on arteriole diameter. Neural activity of dendrites consumes oxygen and leads to a reduction in oxygen pressure, which occurs before
the increase in cerebral blood flow and stimulates glycolysis, causing increased lactate release. Lactate, being vasoactive, can dynamically alter microvasculature diameter in an oxygen-
dependent manner. Vasodilation thus occurs in the brain region experiencing low oxygen tension. Extracellular lactate reduces transporter-mediated uptake from the external space of PGE2.
Manipulating this metabolic circuit may represent a therapeutic strategy for treating the decline in cerebral blood flow associated with some dementias and after stroke. The authors were able
to reliably measure extracellular lactate levels using our L-Lactate Assay Kit (cat#: A-108S and A-108L). Please note that a D-Lactate Assay Kit has recently become available. Additional
citations of our L-Lactate Assay Kit are listed below.
J Pharmacol Exp Ther, 333:341-50, 2010
PLoS One, 5:e13820, 2010
Am J Physiol, 294:E148-E156, 2008
J Fish Biol, 72:1831-1840, 2008
J Biol Chem, 282:1607-14, 2007
J Bacteriol, 189:8079-87, 2007
J Biol Chem, 281:26769-26773, 2006
Proc Natl Acad Sci USA, 103, 18751-18756, 2006
Zaki M, Andrew N, & Insall RH
Entamoeba histolytica cell movement: A central role for self-generated chemokines and chemorepellents
This interesting work by Zaki et al sought to understand the mechanism governing motility of E. histolytica, the cause of amoebic dysentery, within the G.I. tract. It is estimated that ~50 million
people worldwide suffer the severe morbidity caused by E. histolytica, with ~100,000 deaths each year. The authors discovered that components of E. histolytica-conditioned culture medium
are key determinants of cell motility. Using an improved chemotaxis assay, they identified the key extracellular signals mediating Entamoeba chemotaxis. Medium conditioned by E. histolytica
caused both chemokinesis and negative chemotaxis. Random movement was accelerated in conditioned compared with fresh medium, and cells moved efficiently away from conditioned
medium by negative chemotaxis. Ethanol, the product of Entamoeba glucose metabolism, is the principal component of the chemokinetic response. Since the nonpathogenic Entamoeba dispar
does not show such behavior, this finding suggests that negative chemotaxis may play a key role in E. histolytica pathogenesis. Using our Ethanol Assay Kit (cat#: A-111), the authors were
able to confirm that the chemokinetic but not the chemotactic effect of conditioned medium could be completely recreated by physiological ethanol levels. Related assay kits offered by us
include Alcohol Dehydrogenase Assay Kit and Aldehyde Dehydrogenase Assay Kit. Additional citations of our Ethanol Assay kit are listed below.
Cereal Chemistry, 85:322-328, 2008
Alcoholism, 34:997-1005, 2010
J Biol Chem, 286:99-113, 2011
Giulivi C, Ross-Inta C, Omanska-Klusek A, Napoli E, Sakaguchi D, Barrientos G, Allen PD, & Pessah IN
Basal bioenergetic abnormalities in skeletal muscle from ryanodine receptor malignant hyperthermia-susceptible R163C knock-in mice
Malignant hyperthermia (MH), a genetic disorder of skeletal muscle associated with mutations in the ryanodine receptor (RyR1), is characterized by an abnormal response to muscle
depolarizing muscle relaxants. This insightful study focused metabolic differences in MH susceptible and normal skeletal muscle under basal conditions using C57BL6 WT mice and C57BL6
knock-in mice expressing the R163CRyR1 mutation, which is one of the most common human MH mutations. They found that the R163C skeletal muscle exhibited a significant increase in
matrix Ca2+, increased ROS production, and lower expression of mitochondrial proteins. Using our Glyceraldehyde-3-Phosphate (GAPDH) Dehydrogenase Assay Kit (cat#: E-101), they
were able to demonstrate that these changes are associated with lower GAPDH expression and activity. Lower glucose utilization thus suggested a switch to an energy inefficient state
characterized by both low oxidative phosphorylation and glycolysis. Other glycolytic enzymes can be studied using our Hexokinase Assay Kit, Lactate Dehydrogenase Assay Kit, and Glucose
Assay Kit. Additional citations of our GAPDH Assay kit are listed below.
Gynecol Oncol, 107:450-457, 2007
Mol Cell Biochem, 321:45-52, 2009
J Orthopedic Res, 28:914-920, 2010
Cancer Res, 66:1684-1693, 2006
Dang DT, Chen F, Gardner LB, Cummins JM, Rago C, Bunz F, Kantsevoy SV, & Dang LH
Hypoxia-inducible factor-1α promotes nonhypoxia-mediated proliferation in colon cancer cells and xenografts
The hypoxia-inducible transcription factor HIF-1α is strongly associated with cancer cell growth and survival. Although HIF-1α expression is correlated with patient mortality, HIF-1α-deficient
tumors can paradoxically grow faster than their wild-type counterparts. In this article, the authors disrupted HIF-1α by targeted homologous recombination in HCT116 and RKO human colon
cancer cells, and elegantly show that HIF-1α promotes nonhypoxia-mediated cell proliferation in vitro and in vivo in a subset of colon cancers. Using our ATP Assay Kit (cat#: A-107), they
measured levels of ATP and other metabolites in glycolysis under normoxic culture conditions, and found that loss of HIF-1α induced significant decreases in intracellular ATP. An interesting
clinical implication from the work is that therapy targeting HIF-1α may be effective against tumors in which HIF-1α contributes to nonhypoxic cell proliferation. The authors also used our L-
Lactate Assay Kit and LDH Assay Kit. Additional citations of our ATP Assay Kit are listed below.
Mol Cancer, 9:293-304, 2010
J Ethnopharmacol, 130: 614-620, 2010
Phytotherapy Research, in press, 2011
Eur J Pharmacol, 627: 85-91, 2010
J Mol Cell Cardiol, 45:385-393, 2008
Chiu J, Farhangkhoee H, Xu BY, Chen S, George B, & Chakrabarti S
PARP mediates structural alterations in diabetic cardiomyopathy
Diabetic cardiomyopathy is a unique disease that directly affects the structure and the function of the myocardium in the absence of coronary artery disease or hypertension. Increased
oxidative stress from chronic hyperglycemia may have a causative role in the disease progression involving activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP). The
authors investigated the role of PARP in the development of structural changes in the diabetic heart, and determined whether these changes might be mediated by p300, a histone
acetyltransferase. Two models of diabetic complications were used to determine the role of PARP in oxidative stress and fibrosis in the heart. Using our Catalase Assay Kit (cat#: E-100), the
authors demonstrated that hyperglycemia caused upregulation of extracellular matrix proteins and p300 and increased oxidative stress. Specifically, the PARP−/− control mice had significantly
lower catalase activities compared to the WT controls. This study thus nicely illustrates a PARP- and p300-dependent mechanism contributing to the development of structural alterations in the
diabetic heart. Related assay kits offered by us include Peroxide Assay and Lipid Peroxidation Assay Kits. Additional citations of our Catalase Assay Kit are listed below.
PLoS One, 5:e12427, 2010
Cancer Res, 69: 5560-5567, 2009
Cancer Res, 69:5560-5567, 2009
Lynch J, Fukuda Y, Krishnamurthy P, Du G, & Schuetz JD
Cell survival under stress is enhanced by a mitochondrial ATP-binding cassette transporter that regulates hemoproteins
The ATP-binding cassette (ABC) transporter ABCB6 gene is amplified in camptothecin-resistant cells, and its overexpression is associated with multiagent resistance. The authors showed that
increased ABCB6 expression alters the levels of cellular hemoproteins and provides a cell survival advantage. Using our Lactate Dehydrogenase (LDH) Assay Kit (cat#: E-107) to
determine the activity of cytosolic LDH, they showed that increased heme in ABCB6-expressing cells did not alter the expression of either mitochondrial or cytosolic proteins. The ABCB6
overexpressor was not found to be resistant to cytotoxic challenge, but was resistant to cyanide and hydrogen peroxide stress. Thus, the effect of ABCB6 upregulation on multiple
hemoproteins may promote acquisition of multiagent resistance. This dominant effect of ABCB6 has implications for mitochondrial diseases related to defects in cytochrome c oxidase and for
other biochemical processes dependent on heme synthesis. Additional assay kits relevant in the study of glucose metabolism include Hexokinase Assay Kit, L-Lactate Assay Kit, D-Lactate
Assay Kit, G6PD Assay Kit, and Glucose Assay Kit. Additional citations of our LDH Assay kit are listed below.
Cancer Res, 66:1684-1693, 2006
J Anim Sci, 87:3124-3133, 2009
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Biomedical Research Service
& Clinical Application
& Clinical Application
