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Germ cell development is dependent upon the delivery of essential nutriments such as lactate originating from Sertoli cells. Lactate production is under the systemic control but probably also under a local control exerted via certain growth factors. By using a model of porcine cultured Sertoli cells, we have characterized the action of epidermal growth factor (EGF) on lactate production and further delineated the potential biochemical mechanisms involved in the EGF action. EGF stimulated lactate production in a time and dose dependent manner with a half-maximal (ED50) and maximal effects, respectively with 3.8 (0.6 x 10(-9) M) and 22 ng/ml of EGF. Lactate formation involves several biochemical steps among which the glucose substrate uptake and transport system as well as the lactate dehydrogenase (LDH) activity appear to play key roles. We report here that EGF increased the uptake of glucose evaluated through that of 2-deoxy-D-glucose (2-DOG), a non-metabolizable glucose analog. Such an increase in glucose substrate uptake occurs both after a long term (48 h) and a short term treatment (ED50 = 6.4 ng/ml, 1.1 x 10(-9) M EGF). Moreover, EGF was also able to enhance the activity of the Sertoli cell LDH. The maximal effect of the growth factor on LDH activity was observed after a long term (24 h) treatment with an ED50 of 7 ng/ml (1.2 x 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 Mar
PMID:Effect of epidermal growth factor/transforming growth factor alpha on lactate production in porcine Sertoli cells: glucose transport and lactate dehydrogenase isozymes as potential sites of action. 847 66

Lactic acid bacteria are industrial microorganisms used in many food fermentations. Lactococcus species are susceptible to bacteriophage infections that may result in slowed or failed fermentations. A substantial amount of research has focused on characterizing natural mechanisms by which bacterial cells defend themselves against phage. Numerous natural phage defense mechanisms have been identified and studied, and recent efforts have improved phage resistance by using molecular techniques. The study of how phages overcome these resistance mechanisms is also an important objective. New strategies to minimize the presence, virulence, and evolution of phage are being developed and are likely to be applied industrially.
Mol Biotechnol 1995 Dec
PMID:Bacteriophage resistance in Lactococcus. 868 Sep 35

The aim of this study was to examine the effects of chronic low frequency stimulation on the lactate transport across the plasma membrane of the tibialis anterior (TA) muscle of the rat. Stimulating electrodes were implanted on either side of the peroneal nerve in one hindlimb. Chronic stimulation (10 Hz, 50 microsecond bursts, 24h/day) commenced 7 days after surgery, and were continued for 7 days. Animals were then left for 24 h, and thereafter muscles were obtained. Cytochrome C-oxidase activity was increased 1.9-fold in the stimulated TA compared to the control TA (p < 0.05). Lactate transport (zero-trans) was measured in giant sarcolemmal vesicles obtained from the chronically stimulated TA and the control TA. At each of the concentrations used in these studies a significant increase in lactate transport was observed; 2.8-fold increase at 1 mM lactate p < 0.05); 2-fold increases at both 30 mM and 50 mM lactate p < 0.05). These studies have shown that lactate transport capacity is markedly increased in response to chronic muscle contraction.
Mol Cell Biochem 1996 Mar 09
PMID:Chronic muscle stimulation increases lactate transport in rat skeletal muscle. 870 76

The ability of ischemic preconditioning (IP) to protect the myocardium against prolonged ischemia may derive from improved energy balance. We therefore examined myocardial energy metabolism and mitochondrial oxidative phosphorylation in isolated perfused rat hearts which were either subjected (IP group), or not subjected (control group), to preconditioning prior to 30 min sustained ischemia and 30 min reperfusion. Preconditioning was achieved with two cycles of 5 min ischemia followed by 5 min reperfusion. Recovery of myocardial function was significantly greater, and creatine kinase release was significantly lower, in the IP group. Although ATP hydrolysis during the sustained ischemia remained unchanged in both groups, greater preservation of high energy phosphate (eg. ATP and CP) was observed in the IP group after reperfusion. CP content immediately after preconditioning greatly exceeded pre-ischemic values. Lactate production during the sustained ischemia was significantly lower in the IP group, suggesting a decrease in anaerobic glycolysis and a probable attenuation of intracellular acidosis. Oligomycin-sensitive mitochondrial ATPase activity in the control group was significantly decreased both after the sustained ischemia and the reperfusion, but in the IP group it did not change after the preconditioning, sustained ischemia, or reperfusion. Although atractyloside-inhibitable adenine nucleotide translocase activity was markedly decreased during sustained ischemia in both groups, its activity was significantly higher after reperfusion in the IP group. These data suggest that (1) mitochondrial ATPase contributes only slightly to ATP depletion during sustained ischemia, (2) both the CP overshoot phenomenon and the decrease in anaerobic glycolysis can be attributable to cardioprotection during the sustained ischemia, and (3) the preservation of ATPase and adenine nucleotide translocase activities may be a possible explanation for the restoration of high energy phosphates after sustained ischemia-reperfusion injury in the preconditioned hearts of rats.
J Mol Cell Cardiol 1996 Feb
PMID:Effect of ischemic preconditioning on mitochondrial oxidative phosphorylation and high energy phosphates in rat hearts. 872 72

The aims of this study were (1) to determine the characteristics of preconditioning against contractile dysfunction in a blood perfused isolated heart model in the presence of a physiologic combination of substrates, and (2) to determine if protein kinase C (PKC) is involved in preconditioning in this model. In order to investigate these aims, isolated isovolumic, blood perfused rat hearts (balloon-in-LV, n = 6/group) were perfused normoxically for 30 min and then divided into three groups and subjected to: (1) a further 30 min of perfusion (control group) (2) a further 20 min of perfusion + 5 min of ischaemia and 5 min of reperfusion (1 x preconditioned group) and (3) 3 x (5 min of ischaemia+5 min of reperfusion) (3 x preconditioned group). All hearts were then subjected to 30 min of ischaemia and 30 min of reperfusion. Contractile function, myocardial oxygen consumption (MVO2), lactate release and creatine kinase release were all assessed. To determine if PKC is involved in the mechanism of preconditioning in this model, the control and 3 x preconditioned group experiments were repeated in the presence of polymyxin B (50 microM), a relatively specific PKC inhibitor. Final recovery of LVDP was 31 +/- 12, 67 +/- 6 and 60 +/- 5% in the control, 1 x and 3 x preconditioned groups, respectively. Protection of contractile function was accompanied by both a preservation of diastolic function and the ratio of MVO2 to contractile function (ratio of metabolic:mechanical efficiency). However, lactate release was decreased only in the 3 x preconditioned group. Polymyxin B abolished preconditioning-induced protection against contractile and diastolic dysfunction and the protection of the ratio of MVO2 to contractile function. Lactate release was still however reduced in the polymyxin B-preconditioned group. Thus, preconditioning-induced protection against contractile dysfunction appears to be accompanied by a preservation of both diastolic function and the metabolic: mechanical efficiency and is effective in the presence of a physiologic combination of substrates. However, limitation of glycolysis during ischaemia, as assessed by lactate release, appears to be an epiphenomenon of the preconditioning protocol and is not consistently related to protection. PKC activation appears to be pivotal to the mechanism of protection against contractile dysfunction, since administration of polymyxin B abolished any protection.
J Mol Cell Cardiol 1996 May
PMID:Polymyxin B, a protein kinase C inhibitor, abolishes preconditioning-induced protection against contractile dysfunction in the isolated blood perfused rat heart. 876 36

We studied the effect of 12-36 min of global ischemia followed by 36 min of reperfusion in Langendorff perfused rabbit hearts (n = 26). Metabolism was determined in terms of peak and total release of purines (adenosine, inosine, hypoxanthine), lactate and noradrenaline during reperfusion; and myocardial content of nucleotides (ATP, ADP, AMP), glycogen and noradrenaline at the end of reperfusion. An inverse relationship (r = -0.79) existed between duration of ischemia and developed pressure post-ischemia. Early during reperfusion, after 12 min of ischemia, the purine concentration (peak release) increased 100x (p < 0.01), that of lactate and noradrenaline 10x (p < 0.05). Total purine release rose with progression of the ischemic period (30x after 36 min of ischemia; p < 0.01), concomitant with a reduction in nucleotide content. Lactate release was independent from the duration of ischemia, although glycogen had declined by 30% (p < 0.01) after 36 min of ischemia. The acid insoluble glycogen fraction, which presumably contains proglycogen, increased substantially during short-term ischemia. Peak noradrenaline increased 100x, and 200x, (p < 0.05) after 24 and 36 min of ischemia, respectively. Total noradrenaline release due to various periods of ischemia mirrored its peak release. Function recovery was inversely related to total purine and noradrenaline efflux (both r = -0.81); it correlated with tissue nucleotide content (r = 0.84). In conclusion, larger amounts of noradrenaline are released only after a substantial drop in myocardial ATP. During severe ischemia ATP consumption more than limited ATP production by anaerobic glycolysis, is a key factor affecting recovery on subsequent reperfusion. In contrast to lactate efflux, purine and noradrenaline release are useful markers of ischemic and reperfusion damage.
Mol Cell Biochem
PMID:Relation between energy metabolism, glycolysis, noradrenaline release and duration of ischemia. 890 73

Familial dysautonomia (FD), an autosomal recessive disease mapped to chromosome 9q31, is a sensory and autonomic neuropathy of unknown etiology. We have previously reported light microscopic pleiomorphic changes in cells suggestive of altered plasma membranes, an increase in globotriaosylceramide (Gb3), reflected by an increase in Gb3 on the surface of the plasma membrane, and a decrease in the rate and amount of ganglioside synthesized. In unrelated studies, we demonstrated that storage of glycospingolipids (GSL) is deleterious to mitochondrial function. Recently, mitochondrial dysfunction has been associated with neurodegenerative disease, superimposed on an autosomal inheritance pattern. We have now probed Southern blots of total FD fibroblast DNA, digested with BamHI, EcoRII, and/or PvuII, with purified placental 32P-labeled mitochondrial DNA. The sizes of all FD mitochondrial DNAs were normal (16,569 bp), some containing previously identified BamHI polymorphisms. Lactate/pyruvate ratios, and activities of Complexes II and III, matched those of control cells. Electron microscopy revealed morphologically normal mitochondria, in conjunction with a normal oxidative state, determined using the redox dyes Mito Tracker CMXR and CMXR-H2 and fluorescence microscopy. We conclude that mitochondrial dysfunction, due to GSL accumulation, changes in mitochondrial DNA, or mutation of a chromosome 9q gene involved in mitochondrial function, is neither a primary nor a secondary cause of FD, as determined by a study of FD fibroblasts.
Biochem Mol Med 1996 Oct
PMID:Normal mitochondrial DNA and respiratory chain activity in familial dysautonomia fibroblasts. 890 89

Airway epithelial cells cultured at the air-liquid interface possess highly differentiated functions and structures compared with the cells cultured under immersion. We examined the oxidative metabolism and glycolysis in cow tracheal epithelial cells on Days 3, 6, 10, and 13, cultured under three different conditions: (1) immersion culture on porous filters with apical and basolateral feeding (IM), (2) air-exposed culture on porous filters with basolateral feeding, i.e., air-liquid interface culture (AI), and (3) conventional immersion culture in plastic dishes with apical feeding (DI). Lactate production was less in AI than in IM and DI on Day 3 through Day 13, whereas cellular adenosine triphosphate content and basal O2 consumption were greater. Ouabain-sensitive and ouabain-insensitive O2 consumption, and the uncoupled O2 consumption were also greater in AI. Cytosolic lactate dehydrogenase activities on Day 10 were lower in AI, whereas alpha-ketoglutarate dehydrogenase activities were higher. The increased oxidative metabolism in AI was more pronounced at the late phase of culture (Days 10 and 13). In contrast, glycolysis remained elevated during the experiment in IM and DI. These data suggest that (I) AI begins to promote oxidative metabolism from growth phase by the provision of adequate oxygenation, and then further shifts to oxidative metabolism with differentiation; and (2) apical feeding may be responsible for the disturbance of the development of the oxidative metabolism.
Am J Respir Cell Mol Biol 1997 Jan
PMID:Increased oxidative metabolism in cow tracheal epithelial cells cultured at air-liquid interface. 899 80

The concentration dependence of the effects of diltiazem on glycogenolysis, glycolysis, gluconeogenesis and oxygen uptake was investigated in the isolated perfused rat liver. The effects of this compound were very complex. At low concentrations diltiazem increased glycolysis, glycogenolysis (up to 200 microM) and oxygen uptake (up to 100 microM) in livers from fed rats. At the concentrations of 500 and 750 microM the drug inhibited glycolysis, glycogenolysis and oxygen uptake. In livers from fasted rats diltiazem inhibited gluconeogenesis from pyruvate. Inhibition was virtually complete at a concentration of 500 microM. Lactate production from pyruvate and oxygen uptake were also inhibited. Several alterations were observed after cessation of the infusion of diltiazem (i.e., a posteriori effects). The most prominent of these effects was an activation of glucose release in livers from fed rats (glycogenolysis), which occurred after cessation of the infusion of 500 or 750 microM diltiazem. It can be concluded that diltiazem is primarily an inhibitor of energy metabolism in the liver. At high concentrations it blocks the respiratory chain. At low concentrations it could be acting as an uncoupler, because inhibition of a biosynthetic process (gluconeogenesis) occurred at concentrations (up to 200 microM) that simultaneously increased oxygen uptake and glycolysis.
Res Commun Mol Pathol Pharmacol 1996 Dec
PMID:Concentration dependence of the metabolic effects of diltiazem in the isolated perfused rat liver. 902 76

Energy substrate preferences of bovine cleavage-stage embryos produced by in vitro maturation and in vitro fertilization were examined in a chemically-defined (protein-free) culture medium modified hamster embryo culture medium-3, (mHECM3). Few inseminated ova cleaved without energy substrates. Glucose and/or glutamine could not support embryo development, but lactate alone was effective (37% 5-8-cells), equivalent to complex medium TCM-199 (44%). Addition of 11 selected amino acids to lactate increased embryo cleavages, although this treatment was not significantly different from pyruvate alone. Addition of glucose to lactate or to pyruvate depressed development. Lactate + amino acids was significantly better than TCM-199 (54% and 26% > or = 8-cells, respectively). Blastocyst development was evaluated after transferring > or = 8-cell embryos into a complex medium (TCM-199) containing serum. Cleavage-stage embryos produced with pyruvate alone or with lactate + amino acids yielded the highest proportions of blastocysts (36% and 41%, respectively, of inseminated ova). Between 33-63% of blastocysts derived from embryos that were initially developed in mHECM-3 supplemented with various substrates escaped from their zonae (hatched) depending on the treatment, but none of the embryos from the pyruvate + glucose combination hatched. This study shows that optimal energy substrates for bovine cleavage-stage embryo development can be determined using a chemically-defined culture medium, that a simple medium with selected substrates can support early development as well as or better than a complex medium, that a two-step culture system can be used to evaluate blastocyst development from these cleavage-stage embryos, and that timing and hatching of embryos may provide additional information about discriminating between the suitabilities of different substrates for early embryo development.
Mol Reprod Dev 1996 Jun
PMID:Energy substrate requirements for in vitro development of early cleavage-stage bovine embryos. 911 17


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