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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In vivo low density protein (LDL) oxidation is a progressive phenomenon leading to the presence of minimally and highly oxidized LDLs in the subendothelial arterial space. Oxidized LDLs have been reported to be cytotoxic against endothelial cells. The goal of this study was to determine which of the minimally and highly oxidized LDLs were the most cytotoxic against bovine aortic endothelial cells (BAEC). Both the morphological aspect of the cells themselves, and LDH or MTT tests revealed that mO- or Cu-LDLs had similar cytotoxicity with up to 8 hours of oxidation, showing no relation with the level of LDL oxidation; for longer oxidation times, Cu-LDL cytotoxicity decreased. This phenomenon is linked to their different oxidation kinetics. Moreover, in the initial hours following BAEC incubation with mO- or Cu-LDLs, total cell glutathione dropped, whereas after 16 hours of incubation, highly oxidized Cu-LDL increased the glutathione level in the cell. The biphasic evolution of glutathione concentration corresponds to an autoprotective mechanism of cells against oxidized LDL cytotoxicity. This study suggests that the specific chemical characteristics of the different types of oxidized LDLs should always be precisely described in future assays devoted to studying the biological effects of what are known under the generic term as "oxidized LDLs". This precaution should prevent any confusion in interpreting different studies.
J Biochem Mol Toxicol 1999
PMID:Differential toxicities of air (mO-LDL) or copper-oxidized LDLs (Cu-LDL) toward endothelial cells. 1048 19

Smokeless tobacco usage is a growing public health concern in the United States. Lesions of the oral cavity have been clearly linked to smokeless tobacco use. The objective of this study was to determine the biochemical effects of smokeless tobacco extract (STE) exposure upon hamster cheek pouch cell (HCPC-1) cultures. HCPC-1 cells were exposed to a 5 -fold dose-range of STE (0.5, 1.0 and 2.5%) over a time-course of 24-96 h. Following each exposure we measured various biochemical parameters of cell proliferation and cell death. Cell viability, cell cycle progression and S-phase DNA synthesis were measured as markers of cell proliferation. We measured lactate dehydrogenase leakage as a marker of cell membrane damage and cell death due to necrosis. No significant alterations were observed in cell cycle progression and cell proliferation as a result of exposure to STE. LDH measured colorimetrically indicated no significant effect with the lower doses(0.5, 1.0 and 2.5% STE). Apoptosis measured as the A0 peak and by the TUNEL procedure revealed that STE caused significant rates of apoptosis. Maximal apoptosis was noted between 48-96 h. In order to probe the mechanism further we measured the levels of nitrites as an indicator of nitric oxide (NO) in the media. NO levels were significantly elevated at the doses that caused an induction of apoptosis. The results from this study indicate that STE causes a dose-dependent induction of apoptosis and that this is mediated by nitric oxide.
Mol Cell Biochem 1999 Oct
PMID:Role of nitric oxide in the induction of apoptosis by smokeless tobacco extract. 1056 83

Astronotus ocellatus is one of the most hypoxia tolerant fish of the Amazon; adult animals can tolerate up to 6 h of anoxia at 28 degrees C. Changes in energy metabolism during growth have been reported in many fish species and may reflect the way organisms deal with environmental constraints. We have analyzed enzyme levels (lactate dehydrogenase, LDH: EC 1.1.1.27; and malate dehydrogenase, MDH: EC 1.1.1.37) in four different tissues (white muscle, heart, liver, and brain) from different-sized animals. Both enzymes correlate with body size, increasing the anaerobic potential positively with growth. To our knowledge, this is the first description of scaling effects on hypoxia tolerance and it is interesting to explore the fact that hypoxia survivorship increases due to combining effects of suppressing metabolic rates and increasing anaerobic power as fish grow.
Comp Biochem Physiol B Biochem Mol Biol 2000 Feb
PMID:Scaling effects on hypoxia tolerance in the Amazon fish Astronotus ocellatus (Perciformes: Cichlidae): contribution of tissue enzyme levels. 1081 9

Radiation inactivation of sperm specific lactate dehydrogenase-C4 (LDH-C4) has been studied and compared with the somatic LDH in aqueous solution. D37 of C isozyme was 470 Gy and that of B isozyme was 520 Gy. Semi-log plots of log N/No versus dose suggested that the inactivation of two LDH isozymes in presence of normal saline follows a single hit kinetics. Target molecular weight calculated by radiation analysis was found as 1.52 x 10(5) gm/mole for LDH-C4 and 1.38 x 10(5) gm/mole for LDH-B4. SDS-PAGE of irradiated enzymes showed a band of 35 kDa but did not indicate the presence of any other extra band, when compared with sham-irradiated enzymes. Chemical kinetics of residual activity following irradiation at D37 showed decrease in Vmax with coenzymes and primary substrates. However, decrease in Km was seen with pyruvate as increasing substrate. Nevertheless, K did not change when NAD+ was the leading substrate for LDH-B4 or LDH-C4. A hyperchromicity in intrinsic fluorescence and a blue shift in lambdamax over sham-irradiated LDH-C4 revealed the exposure of buried tryptophan residues to the surface after radiation inactivation. Results suggest that inspite of presence of variant amino acids, the conformations of two isozymes are stabilized by similar forces which behave in a similar way for radiation inactivation in aqueous phase.
Mol Cell Biochem 2000 Mar
PMID:Molecular and kinetic properties of sperm specific LDH after radiation inactivation. 1083 91

Clusterin has been known to play important roles in cell-cell and/or cell-substratum interactions. Recently we reported the transient expression of clusterin in pancreatic endocrine cells during the early developmental stages and suggested a role in aggregating the endocrine cells for islet formation. In the present study, we have investigated the involvement of clusterin in cell-substratum interaction by the inhibition of clusterin synthesis using antisense oligonucleotide. The expression of clusterin was transiently increased as early as 2-8 h after plating the ASC-17D Sertoli cells to the culture flask, which was the period of cell attachment. In addition, up-regulation of clusterin mRNA was so much greater when the Sertoli cells were plated on the petri dish for the bacterial culture instead of in a animal cell culture flask that therefore, the cells failed to attach to it. These findings suggested that interruption of cell to plate substratum interaction might lead to over-expression of clusterin from Sertoli cells to induce cell to cell aggregation or, perhaps, to re-establish attachment with the substratum. Transfection of ASC-17D Sertoli cells with a 20-base antisense oligonucleotide against clusterin mRNA resulted in extracellular release of LDH and DNA fragmentation. Sertoli cell death by antisense oligonucleotide of clusterin was sequence specific and dose dependent. Treatment of antisense oligonucleotide induced a marked reduction of synthesis for clusterin protein, but not for clusterin mRNA expression, suggesting the translational suppression of clusterin by antisense oligonucleotide. Further, microscopic observation showed that more noticeable cell death was induced by treating the antisense prior to plating the cells than by treating after cell attachment to the plate. From these results, we speculate that down-regulation of clusterin expression in the anchorage-dependent Sertoli cells prevents them from attaching to the plate, and therefore induces cell death.
Mol Cells 2000 Apr 30
PMID:Antisense oligonucleotide of clusterin mRNA induces apoptotic cell death and prevents adhesion of rat ASC-17D Sertoli cells. 1085 Jun 61

Estimation of gene trees is the first step in testing alternative hypotheses about the evolution of multigene families. The standard practice for inferring gene family history is to construct trees that meet some objective criteria based on the fit of the character state changes (nucleotide or amino acid changes) to the gene tree. Unfortunately, analysis of character state data can be misleading. In addition, this approach ignores information about the relationships of the species from which the genes have been sampled. In this paper I explore using statistics of fit between the character data and gene trees and the reconciliation of the gene and species trees for choosing among alternative evolutionary hypotheses of gene families. In particular, I advocate a two-pronged strategy for choosing among alternative gene trees. First, the character data are used to define a set of acceptable gene trees (i.e., trees that are not significantly different from the minimum length tree). Next, the set of acceptable gene trees is reconciled with a known species tree, and the gene tree requiring the fewest number of gene duplications and losses is adopted as the best estimate of evolutionary history. The approach is illustrated using three gene families: BMP, EGR, and LDH.
Mol Phylogenet Evol 2000 Sep
PMID:Choosing among alternative trees of multigene families. 1099 95

Saduria entomon lactate dehydrogenase (LDH-A4*) from thorax muscle was purified about 89 fold to specific activity 510 micromol NADH/min/mg using Cibacron Blue 3GA Agarose and Oxamate-Agarose chromatographies. The enzyme is a tetramer, with molecular weight of 140 kDa for the native enzyme and 36 kDa for the subunit. The isoelectric point was at pH 5.7. The enzyme possesses high heat stability (T50 = 71.5 degrees C). The optimum pH for pyruvate reduction reaction was 6.5, while for lactate oxidation one, the maximum activity was at pH 9.1. The Km for pyruvate was minimal at 5 degrees C, the average environmental temperature of the isopod. The Km values determined at 30 degrees C and optimal pH for pyruvate reduction and lactate oxidation were 0.18 and 90.04 mM, respectively. Amino acid compositional analyses showed the strongest resemblance of the isopod isoenzyme to cod (Gadus morhua) LDH-C4.
Comp Biochem Physiol B Biochem Mol Biol 2000 Jul
PMID:Properties of lactate dehydrogenase from the isopod, Saduria entomon. 1100 75

Scarce bibliographical data exists on the enzymes in Lepidosiren paradoxa and analysis of several enzymes was considered worthy of investigation. Distribution of ADH, ALP, FBALD, GAPDH, G3PDH, G6PDH, GPI, LDH, MDH, and PGM was identified in ten tissues (retina, heart, muscle, liver, kidney, lung, gut, gills, brain, and ovary) of the South American lungfish and compared with patterns previously described in other vertebrates. Compared with earlier results differences in the number of loci expressed were observed for ADH, G3PDH, GPI, and MDH. The number of loci expressed and/or in tissue specificity of several enzymes (ADH, FBALD, GAPDH, G3PDH, G6PDH and PGM) were found to be similar to those of other vertebrates. Differences were detected in ALP due to the absence of an intestinal-specific form typical of fish, amphibians, reptiles and birds; further differences were observed in GPI and MDH due to their tissue expression. The differences in LDH involve the LDH-A4 isozyme which was most common in tissues. Overall, comparison with other vertebrates reveals that in L. paradoxa the tissue-restricted expressions of some enzymes are similar, while others have retained an ancestral pattern and exhibit a more widespread tissue expression of genes.
Comp Biochem Physiol B Biochem Mol Biol 2000 Aug
PMID:Isozyme distribution of ten enzymes and their loci in South American lungfish, Lepidosiren paradoxa (Osteichthyes, Dipnoi). 1102 62

Focal cerebral ischemia activates the nuclear protein poly(ADP-ribose) polymerase (PARP) by single DNA strand breaks which leads to energy depletion and cell necrosis. Deletion or inhibition of PARP protects against ischemic brain injury. Here we examined the neuroprotective effect of PJ34, a novel potent inhibitor of PARP in vitro and in vivo. Serum-free primary neuronal cultures derived from rat cortex (E15-17) and kept in culture for 10 days were exposed to oxygen glucose deprivation (OGD) in vitro. Neuronal injury was quantified by LDH release after 24 h. Pretreatment with 30-1000 nM PJ34 significantly protected from OGD-induced cell injury in a dose-dependent manner. For in vivo experiments SV/129 mice were treated with PJ34 (50 microg) by intraperitoneal injection 2 h before 1 h middle cerebral artery occlusion (MCAo) and again 6 h later. Twenty-three h after reperfusion ischemic injury was significantly decreased compared to vehicle-treated controls (infarct volume reduction of 40%, p<0.05). Similarly, in a rat model of MCAo (2 h occlusion followed by up to 22 h reperfusion), PJ34 administration (10 mg/kg i.v.) significantly reduced infarct size, and the effect of the drug was maintained even if it was given as late as 10 min prior to reperfusion time. PJ34 significantly protected in a 4 h, but not in a 24 h permanent occlusion model. In conclusion, PJ34, a novel, potent inhibitor of PARP exerts massive neuroprotective agents, with a significant therapeutic window of opportunity. The present work strengthens the concept that pharmacological PARP inhibition may be a suitable approach for the treatment of acute stroke in man.
Int J Mol Med 2001 Mar
PMID:Protective effects of PJ34, a novel, potent inhibitor of poly(ADP-ribose) polymerase (PARP) in in vitro and in vivo models of stroke. 1117 3

The present study is designed to investigate the role of Na+ -H+ exchanger in the cardioprotective effect of ischaemic and angiotensin (Ang II) preconditioning. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Left ventricular developed pressure (LVDP) and dp/dt were recorded to evaluate myocardial contractility. Four episodes of ischaemic or Ang II preconditioning markedly reduced LDH and CK release in coronary effluent and decreased myocardial infarct size. 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a Na+ - H+ exchange inhibitor, produced no marked effect on ischaemic preconditioning and Ang II preconditioning induced cardioprotection. On the other hand, EIPA administration prior to global ischaemia produced a similar reduction in myocardial injury as was noted with ischaemic preconditioning or Ang II preconditioning. On the basis of these results, it may be concluded that inhibition of Na+ - H+ exchanger protects against ischaemia-reperfusion induced myocardial injury whereas activation of Na+ - H+ exchanger may not mediate the cardioprotective effect of ischaemic and Ang II preconditioning.
Mol Cell Biochem 2000 Nov
PMID:Effect of ethylisopropyl amiloride, a Na+ - H+ exchange inhibitor, on cardioprotective effect of ischaemic and angiotensin preconditioning. 1119 87


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