Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lipid hypothesis stipulates that the risk of developing CAD is related to the cholesterol levels of various lipoprotein fractions, the risk increasing with either a higher LDL cholesterol level or a lower HDL cholesterol level. The data reviewed here indicate that the measurement of the plasma level of the major apoproteins of LDL and HDL, apoB and apoA-I, respectively, provide additional information in the assessment of a patient at risk for CAD. In the case of LDL B, two "normocholesterolemic" groups with CAD are detected, those with normotriglyceridemic HyperapoB and those with hypertriglyceridemic HyperapoB . In all of these syndromes associated with premature CAD, HyperapoB , FCH, and FH, the common denominator is an increased number of LDL particles. A low level of apoA-I may indicate that one of the subfractions of HDL (HDL2) is decreased. HDL2 is generally decreased in disorders where LDL B is elevated, a combination that may be particularly atherogenic. Conversely, elevated apoA-I and HDL cholesterol levels, or decreased LDL cholesterol and LDL B protein levels, are associated with a low prevalence of CAD and longevity. Thus, LDL and HDL levels may be metabolically linked, a relation which is more evident if apoproteins are measured and which may be obscured if apoproteins are not determined. The assessment of dyslipoproteinemia in a patient at risk for CAD might optimally include measurement of LDL B and apoA-I levels, in addition to LDL cholesterol and HDL cholesterol levels.
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PMID:Atherosclerosis and apoproteins B and A-I. 642 65

Ionizing radiation induces chronic metabolic oxidative stress and a mutator phenotype in hamster fibroblasts that is mediated by H(2)O(2), but the intracellular source of H(2)O(2) is not well defined. To determine the role of mitochondria in the radiation-induced mutator phenotype, end points of mitochondrial function were determined in unstable (CS-9 and LS-12) and stable (114) hamster fibroblast cell lines derived from GM10115 cells exposed to 10 Gy X rays. Cell lines isolated after irradiation demonstrated a 20-40% loss of mitochondrial membrane potential and an increase in mitochondrial content compared to the parental cell line GM10115. Surprisingly, no differences were observed in steady-state levels of ATP (P > 0.05). Unstable clones demonstrated increased oxygen consumption (two- to threefold; CS-9) and/or increased mitochondrial electron transport chain (ETC) complex II activity (twofold; LS-12). Using Western blot analysis and Blue Native gel electrophoresis, a significant increase in complex II subunit B protein levels was observed in LS-12 cells. Furthermore, immunoprecipitation assays revealed evidence of abnormal complex II assembly in LS-12 cells. Treatment of LS-12 cells with an inhibitor of ETC complex II (thenoyltrifluoroacetone) resulted in significant decreases in the steady-state levels of H(2)O(2) and a 50% reduction in mutation frequency as well as a 16% reduction in CAD gene amplification frequency. These data show that radiation-induced genomic instability was accompanied by evidence of mitochondrial dysfunction leading to increased steady-state levels of H(2)O(2) that contributed to increased mutation frequency and gene amplification. These results support the hypothesis that mitochondrial dysfunction originating from complex II can contribute to radiation-induced genomic instability by increasing steady-state levels of reactive oxygen species.
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PMID:Mitochondrial complex II dysfunction can contribute significantly to genomic instability after exposure to ionizing radiation. 1992 20