Godfrey Getz - Academia.edu (original) (raw)

Papers by Godfrey Getz

Research paper thumbnail of Naturally occurring variant of mouse apolipoprotein A-I alters the lipid and HDL association properties of the protein

Journal of Lipid Research, May 1, 2012

Research paper thumbnail of An apoA-I mimetic peptide containing a proline residue has greater in vivo HDL binding and anti-inflammatory ability than the 4F peptide

Journal of Lipid Research, Sep 1, 2009

Research paper thumbnail of Isoform-specific effect of apolipoprotein E on cell survival and beta-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures

PubMed, 1998

Although the genetic link between the epsilon4 allele of apolipoprotein E (apoE) and Alzheimer's ... more Although the genetic link between the epsilon4 allele of apolipoprotein E (apoE) and Alzheimer's disease is well established, the isoform-specific activity of apoE underlying this correlation remains unclear. To determine whether apoE influences the neurotoxic actions of beta-amyloid (Abeta), we examined the effect of native preparations of apoE3 and E4 on Abeta-induced toxicity in primary cultures of rat hippocampal pyramidal neurons. The source of apoE was conditioned medium from HEK-293 cells stably transfected with human apoE3 or E4 cDNA. ApoE4 (10 microg/ml) alone was toxic to the cultures, whereas apoE3 had no effect. ApoE3 treatment prevented the toxicity induced by 10 microM Abeta(1-40) or Abeta(25-35). The apoE3 protective effect appears to be specific to Abeta-induced toxicity, because apoE3 did not protect against the cytotoxicity produced by NMDA or staurosporine, nor did apoE3 affect the increase in intracellular calcium induced by either NMDA or KCl. ApoE3 had no effect on the toxicity produced by Abeta in the presence of receptor-associated protein, an inhibitor of apoE receptors, particularly the LDL-receptor-related protein. Interaction with apoE receptors may not mediate the toxic actions of apoE4, because receptor-associated protein did not affect apoE4-induced neurotoxicity. Consistent with our previous biochemical experiments, analysis of the culture medium revealed that SDS-stable apoE3:Abeta complex is present in greater abundance than apoE4:Abeta complex. Thus, the protection from Abeta-induced neurotoxicity afforded by apoE3 treatment may result from clearance of the peptide by apoE3:Abeta complex formation and uptake by apoE receptors.

Research paper thumbnail of Apoprotein A-I mimetic peptides and their potential anti-atherogenic mechanisms of action

Current Opinion in Lipidology, Jun 1, 2009

Research paper thumbnail of Mitochondrial nucleic acids in the peptite colonie mutants: Deletions and repetitions of genes

Research paper thumbnail of Mimetic peptides of human apoA-I helix 10 get together to lower lipids and ameliorate atherosclerosis: is the action in the gut?

Journal of Lipid Research, Oct 1, 2014

Research paper thumbnail of Biological Properties of Apolipoprotein A-I Mimetic Peptides

Current Atherosclerosis Reports, Feb 20, 2010

Research paper thumbnail of 4F Peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E‐null mice

The FASEB Journal, Sep 27, 2010

Our objective was to contrast the effect of apolipoprotein (apo) A-I mimetic peptides, such as 4F... more Our objective was to contrast the effect of apolipoprotein (apo) A-I mimetic peptides, such as 4F and 4F-Pro-4F (Pro), on nascent and mature atherosclerotic lesions and on levels of antibodies against oxidation-specific epitopes. Chow-fed apoE(-/-) mice were injected intraperitoneally with either the 4F peptide or a tandem helix apoA-I mimetic peptide (Pro) every other day. Mice treated with 4F, but not Pro, for 4 wk starting at 10 wk of age showed a dramatic decrease in atherosclerosis at 2 arterial sites. However, neither peptide was effective in mice treated for 8 wk starting at 20 wk of age; lesions were larger and more mature at this time point. Peptide treatment caused increased production of antibodies against oxidation-specific epitopes, including a disproportionate induction of the IgM natural antibody (NAb) E06/T15 to oxidized phospholipids. In summary, 4F, but not the tandem peptide Pro, effectively inhibited early atherogenesis but was ineffective against more mature lesions. Two different apoA-I mimetic peptides increased titers of natural antibodies against oxidation-specific epitopes.

Research paper thumbnail of Isoform-Specific Effect of Apolipoprotein E on Cell Survival and β-Amyloid-Induced Toxicity in Rat Hippocampal Pyramidal Neuronal Cultures

The Journal of Neuroscience, 1998

Research paper thumbnail of Characterization of Yeast Grande and Petite Mitochondrial Dna by Hybridization and Physical Techniques

Research paper thumbnail of Editorial: Diabetes Augmentation on Vascular Disease

Research paper thumbnail of Regulation of transcriptional initiation in yeast mitochondria

Journal of Biological Chemistry, 1990

Research paper thumbnail of The characterization of yeast mitochondrial RNA polymerase. A monomer of 150,000 daltons with a transcription factor of 70,000 daltons

Journal of Biological Chemistry, 1988

Research paper thumbnail of Mechanism of the Growth-related Activation of the Low Density Lipoprotein Receptor Pathway

Journal of Biological Chemistry, 1989

Research paper thumbnail of The intracellular distribution of fatty acids in rat liver. The fatty acids of intracellular compartments

Biochemical Journal, 1961

Research paper thumbnail of Cloning and Sequencing of Guinea Pig Apolipoprotein E cDNA: Possible Pi Helical Conformation on the Conserved Amino Acid Sequence

The Journal of Japan Atherosclerosis Society, 1989

Research paper thumbnail of Genetic control of apoprotein A-I and atheroprotection: some insights from inbred strains of mice

Current Opinion in Lipidology, 2017

Purpose of review Previous epidemiological studies and studies in experimental animals have provi... more Purpose of review Previous epidemiological studies and studies in experimental animals have provided strong evidence for the atheroprotective effect of HDL and its major apoprotein, apolipoprotein A-I (apoA-I). Identification of genetic loci associating apoA-I/HDL with cardiovascular disease is needed to establish a causal relationship. Recent findings Pharmacological interventions to increase apoA-I or HDL cholesterol levels in humans are not associated with reduction in atherosclerosis. Genome wide association study (GWAS) studies in humans and hybrid mouse diversity panel (HMDP) studies looking for genetic variants associated with apoA-I or HDL cholesterol levels with cardiovascular disease and atherosclerosis have not provided strong evidence for their atheroprotective function. Summary These findings indicate that GWAS and HMDP studies identifying possible genetic determinants of HDL and apoA-I function are needed.

Research paper thumbnail of The western-type diet induces anti-HMGB1 autoimmunity in Apoe −/− mice

Research paper thumbnail of Mitochondrial development in liver of foetal and newborn rats

Biochemical Journal, 1971

The development of the inner mitochondrial membrane in foetal and neonatal rat liver was studied ... more The development of the inner mitochondrial membrane in foetal and neonatal rat liver was studied by following three parameters: (1) the activity of several respiratory enzymes in homogenates and purified mitochondria, (2) the spectrophotometric determination of cytochrome content in the mitochondria and (3) the cardiolipin content in both homogenates and purified mitochondria. Respiratory-enzyme activities of homogenates of foetal liver were one-quarter to one-twentieth of those of homogenates of adult liver, and the enzyme specific activities in purified mitochondria from foetal liver were one-half to one-eighth of those in mitochondria from adult liver. The cardiolipin content of liver homogenates increased approximately twofold during the development period, but there was no significant change in the cardiolipin content of purified mitochondria. It is concluded that cell mitochondrial content approximately doubles in the immediate postnatal period. There was no evidence for an in...

Research paper thumbnail of Environmentally induced differential amplification of mitochondrial populations

Biochemical Journal, 1990

Resistance to the drug rutamycin, an inhibitor of mitochondrial ATPase, has been shown to be cyto... more Resistance to the drug rutamycin, an inhibitor of mitochondrial ATPase, has been shown to be cytoplasmically inherited in a mouse fibroblast line (TL) on fusion of the cytoplast (enTL) with a nucleated recipient A9 [Lichtor & Getz (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 324-328]. The cytoplasmic hybrid (cybrid) so formed may be readily grown in the presence [CY(+)] or absence [CY(-)] of rutamycin. The ATPase of TL mitochondria is similarly resistant to rutamycin whether grown in the presence or absence of antibiotic. The ATPase of CY(+) mitochondria is resistant to rutamycin, but CY(-) mitochondrial ATPase is sensitive to rutamycin. Nevertheless, CY(-) can be readily grown in rutamycin after a brief lag. The pH optima of mitochondrial ATPase are 8.0 for A9 and CY(-) cells and 7.5 for TL cells, whereas the pH optimum for CY(+) spans the optima of A9 and TL. The TL mitochondrial NADH-cytochrome c reductase is resistant to rotenone, whereas that of A9 mitochondria is sensitive to this...

Research paper thumbnail of Naturally occurring variant of mouse apolipoprotein A-I alters the lipid and HDL association properties of the protein

Journal of Lipid Research, May 1, 2012

Research paper thumbnail of An apoA-I mimetic peptide containing a proline residue has greater in vivo HDL binding and anti-inflammatory ability than the 4F peptide

Journal of Lipid Research, Sep 1, 2009

Research paper thumbnail of Isoform-specific effect of apolipoprotein E on cell survival and beta-amyloid-induced toxicity in rat hippocampal pyramidal neuronal cultures

PubMed, 1998

Although the genetic link between the epsilon4 allele of apolipoprotein E (apoE) and Alzheimer's ... more Although the genetic link between the epsilon4 allele of apolipoprotein E (apoE) and Alzheimer's disease is well established, the isoform-specific activity of apoE underlying this correlation remains unclear. To determine whether apoE influences the neurotoxic actions of beta-amyloid (Abeta), we examined the effect of native preparations of apoE3 and E4 on Abeta-induced toxicity in primary cultures of rat hippocampal pyramidal neurons. The source of apoE was conditioned medium from HEK-293 cells stably transfected with human apoE3 or E4 cDNA. ApoE4 (10 microg/ml) alone was toxic to the cultures, whereas apoE3 had no effect. ApoE3 treatment prevented the toxicity induced by 10 microM Abeta(1-40) or Abeta(25-35). The apoE3 protective effect appears to be specific to Abeta-induced toxicity, because apoE3 did not protect against the cytotoxicity produced by NMDA or staurosporine, nor did apoE3 affect the increase in intracellular calcium induced by either NMDA or KCl. ApoE3 had no effect on the toxicity produced by Abeta in the presence of receptor-associated protein, an inhibitor of apoE receptors, particularly the LDL-receptor-related protein. Interaction with apoE receptors may not mediate the toxic actions of apoE4, because receptor-associated protein did not affect apoE4-induced neurotoxicity. Consistent with our previous biochemical experiments, analysis of the culture medium revealed that SDS-stable apoE3:Abeta complex is present in greater abundance than apoE4:Abeta complex. Thus, the protection from Abeta-induced neurotoxicity afforded by apoE3 treatment may result from clearance of the peptide by apoE3:Abeta complex formation and uptake by apoE receptors.

Research paper thumbnail of Apoprotein A-I mimetic peptides and their potential anti-atherogenic mechanisms of action

Current Opinion in Lipidology, Jun 1, 2009

Research paper thumbnail of Mitochondrial nucleic acids in the peptite colonie mutants: Deletions and repetitions of genes

Research paper thumbnail of Mimetic peptides of human apoA-I helix 10 get together to lower lipids and ameliorate atherosclerosis: is the action in the gut?

Journal of Lipid Research, Oct 1, 2014

Research paper thumbnail of Biological Properties of Apolipoprotein A-I Mimetic Peptides

Current Atherosclerosis Reports, Feb 20, 2010

Research paper thumbnail of 4F Peptide reduces nascent atherosclerosis and induces natural antibody production in apolipoprotein E‐null mice

The FASEB Journal, Sep 27, 2010

Our objective was to contrast the effect of apolipoprotein (apo) A-I mimetic peptides, such as 4F... more Our objective was to contrast the effect of apolipoprotein (apo) A-I mimetic peptides, such as 4F and 4F-Pro-4F (Pro), on nascent and mature atherosclerotic lesions and on levels of antibodies against oxidation-specific epitopes. Chow-fed apoE(-/-) mice were injected intraperitoneally with either the 4F peptide or a tandem helix apoA-I mimetic peptide (Pro) every other day. Mice treated with 4F, but not Pro, for 4 wk starting at 10 wk of age showed a dramatic decrease in atherosclerosis at 2 arterial sites. However, neither peptide was effective in mice treated for 8 wk starting at 20 wk of age; lesions were larger and more mature at this time point. Peptide treatment caused increased production of antibodies against oxidation-specific epitopes, including a disproportionate induction of the IgM natural antibody (NAb) E06/T15 to oxidized phospholipids. In summary, 4F, but not the tandem peptide Pro, effectively inhibited early atherogenesis but was ineffective against more mature lesions. Two different apoA-I mimetic peptides increased titers of natural antibodies against oxidation-specific epitopes.

Research paper thumbnail of Isoform-Specific Effect of Apolipoprotein E on Cell Survival and β-Amyloid-Induced Toxicity in Rat Hippocampal Pyramidal Neuronal Cultures

The Journal of Neuroscience, 1998

Research paper thumbnail of Characterization of Yeast Grande and Petite Mitochondrial Dna by Hybridization and Physical Techniques

Research paper thumbnail of Editorial: Diabetes Augmentation on Vascular Disease

Research paper thumbnail of Regulation of transcriptional initiation in yeast mitochondria

Journal of Biological Chemistry, 1990

Research paper thumbnail of The characterization of yeast mitochondrial RNA polymerase. A monomer of 150,000 daltons with a transcription factor of 70,000 daltons

Journal of Biological Chemistry, 1988

Research paper thumbnail of Mechanism of the Growth-related Activation of the Low Density Lipoprotein Receptor Pathway

Journal of Biological Chemistry, 1989

Research paper thumbnail of The intracellular distribution of fatty acids in rat liver. The fatty acids of intracellular compartments

Biochemical Journal, 1961

Research paper thumbnail of Cloning and Sequencing of Guinea Pig Apolipoprotein E cDNA: Possible Pi Helical Conformation on the Conserved Amino Acid Sequence

The Journal of Japan Atherosclerosis Society, 1989

Research paper thumbnail of Genetic control of apoprotein A-I and atheroprotection: some insights from inbred strains of mice

Current Opinion in Lipidology, 2017

Purpose of review Previous epidemiological studies and studies in experimental animals have provi... more Purpose of review Previous epidemiological studies and studies in experimental animals have provided strong evidence for the atheroprotective effect of HDL and its major apoprotein, apolipoprotein A-I (apoA-I). Identification of genetic loci associating apoA-I/HDL with cardiovascular disease is needed to establish a causal relationship. Recent findings Pharmacological interventions to increase apoA-I or HDL cholesterol levels in humans are not associated with reduction in atherosclerosis. Genome wide association study (GWAS) studies in humans and hybrid mouse diversity panel (HMDP) studies looking for genetic variants associated with apoA-I or HDL cholesterol levels with cardiovascular disease and atherosclerosis have not provided strong evidence for their atheroprotective function. Summary These findings indicate that GWAS and HMDP studies identifying possible genetic determinants of HDL and apoA-I function are needed.

Research paper thumbnail of The western-type diet induces anti-HMGB1 autoimmunity in Apoe −/− mice

Research paper thumbnail of Mitochondrial development in liver of foetal and newborn rats

Biochemical Journal, 1971

The development of the inner mitochondrial membrane in foetal and neonatal rat liver was studied ... more The development of the inner mitochondrial membrane in foetal and neonatal rat liver was studied by following three parameters: (1) the activity of several respiratory enzymes in homogenates and purified mitochondria, (2) the spectrophotometric determination of cytochrome content in the mitochondria and (3) the cardiolipin content in both homogenates and purified mitochondria. Respiratory-enzyme activities of homogenates of foetal liver were one-quarter to one-twentieth of those of homogenates of adult liver, and the enzyme specific activities in purified mitochondria from foetal liver were one-half to one-eighth of those in mitochondria from adult liver. The cardiolipin content of liver homogenates increased approximately twofold during the development period, but there was no significant change in the cardiolipin content of purified mitochondria. It is concluded that cell mitochondrial content approximately doubles in the immediate postnatal period. There was no evidence for an in...

Research paper thumbnail of Environmentally induced differential amplification of mitochondrial populations

Biochemical Journal, 1990

Resistance to the drug rutamycin, an inhibitor of mitochondrial ATPase, has been shown to be cyto... more Resistance to the drug rutamycin, an inhibitor of mitochondrial ATPase, has been shown to be cytoplasmically inherited in a mouse fibroblast line (TL) on fusion of the cytoplast (enTL) with a nucleated recipient A9 [Lichtor & Getz (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 324-328]. The cytoplasmic hybrid (cybrid) so formed may be readily grown in the presence [CY(+)] or absence [CY(-)] of rutamycin. The ATPase of TL mitochondria is similarly resistant to rutamycin whether grown in the presence or absence of antibiotic. The ATPase of CY(+) mitochondria is resistant to rutamycin, but CY(-) mitochondrial ATPase is sensitive to rutamycin. Nevertheless, CY(-) can be readily grown in rutamycin after a brief lag. The pH optima of mitochondrial ATPase are 8.0 for A9 and CY(-) cells and 7.5 for TL cells, whereas the pH optimum for CY(+) spans the optima of A9 and TL. The TL mitochondrial NADH-cytochrome c reductase is resistant to rotenone, whereas that of A9 mitochondria is sensitive to this...