Fong-fu Hsu - Academia.edu (original) (raw)
Papers by Fong-fu Hsu
Journal of the American Society for Mass Spectrometry, 2021
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Analytica Chimica Acta, 2021
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Biochemical and Biophysical Research Communications, 1990
Phosphoinositide phospholipase C activity was investigated in human melanoma grown as solid tumor... more Phosphoinositide phospholipase C activity was investigated in human melanoma grown as solid tumor xenografts in nude mice. The enzyme was dependent on calcium for activity and was stimulated by the detergent deoxycholate. The pH optimum was 5.5 in the absence of detergent, and in the presence of deoxycholate two pH maxima were present, 5.5 and 7.2. Phospholipase C activity was inhibited by the sulfhydryl reagent dithionitrobenzoate with an IC50 in the micromolar range. Phospholipase C activity was distributed widely in mouse tissues. The enzyme showed a progressive increase in activity from heart, liver, lung, colon, spleen, to brain tissue. Mouse and human melanomas grown as solid tumors had higher phospholipase C activity than mouse brain. The relatively high activity of this enzyme in melanoma may suggest a biological role for phospholipase C in solid tumor growth.
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Journal of Lipid Research, 2021
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Molecular microbiology, Jan 27, 2018
Limited knowledge on the exact functions of ergostane-based sterols has hampered the application ... more Limited knowledge on the exact functions of ergostane-based sterols has hampered the application of sterol synthesis inhibitors against trypanosomatid parasites. Sterol methyltransferase (SMT) is directly involved in the synthesis of parasite specific C24-methylated sterols including ergosterol and 5-dehydroepisterol. While pharmacological studies hint at its potential as a drug target against trypanosomatids, direct evidence for the cellular function and essentiality of SMT is lacking. Here we characterized the SMT knockout mutants and their complemented strains in Leishmania major, the causative agent for cutaneous leishmaniasis. Deletion of SMT alleles led to a complete loss of C24-methylated sterols, which were replaced by cholestane-based sterols. SMT-null mutants were fully viable and replicative in culture but showed increased sensitivity to sphingolipid synthesis inhibition. They were not particularly vulnerable to heat, acidic pH, nitrosative or oxidative stress, yet exhibi...
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Cell Reports, 2017
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Frontiers in Bioscience, 2011
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PLoS pathogens, 2014
Sterol biosynthesis is a crucial pathway in eukaryotes leading to the production of cholesterol i... more Sterol biosynthesis is a crucial pathway in eukaryotes leading to the production of cholesterol in animals and various C24-alkyl sterols (ergostane-based sterols) in fungi, plants, and trypanosomatid protozoa. Sterols are important membrane components and precursors for the synthesis of powerful bioactive molecules, including steroid hormones in mammals. Their functions in pathogenic protozoa are not well characterized, which limits the development of sterol synthesis inhibitors as drugs. Here we investigated the role of sterol C14α-demethylase (C14DM) in Leishmania parasites. C14DM is a cytochrome P450 enzyme and the primary target of azole drugs. In Leishmania, genetic or chemical inactivation of C14DM led to a complete loss of ergostane-based sterols and accumulation of 14-methylated sterols. Despite the drastic change in lipid composition, C14DM-null mutants (c14dm(-)) were surprisingly viable and replicative in culture. They did exhibit remarkable defects including increased me...
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Cell Metabolism, 2015
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The Journal of Neuroscience, 2006
It has been postulated that the development of amyloid plaques in Alzheimer's disease (AD) ma... more It has been postulated that the development of amyloid plaques in Alzheimer's disease (AD) may result from an imbalance between the generation and clearance of the amyloid-β peptide (Aβ). Although familial AD appears to be caused by Aβ overproduction, sporadic AD (the most prevalent form) may result from impairment in clearance. Recent evidence suggests that several proteases may contribute to the degradation of Aβ. Furthermore, astrocytes have recently been implicated as a potential cellular mediator of Aβ degradation. In this study, we examined the possibility that matrix metalloproteinases (MMPs), proteases known to be expressed and secreted by astrocytes, could play a role in extracellular Aβ degradation. We found that astrocytes surrounding amyloid plaques showed enhanced expression of MMP-2 and MMP-9 in aged amyloid precursor protein (APP)/presenilin 1 mice. Moreover, astrocyte-conditioned medium (ACM) degraded Aβ, lowering levels and producing several fragments after incu...
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The EMBO Journal, 2007
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Molecular Microbiology, 2005
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Molecular Microbiology, 2013
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Journal of Molecular and Cellular Cardiology, 2002
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Journal of Medicinal Chemistry, 1997
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Journal of Biological Chemistry, 1996
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Journal of Biological Chemistry, 1996
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Journal of Biological Chemistry, 1999
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Journal of Biological Chemistry, 2001
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Journal of Biological Chemistry, 1999
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Journal of the American Society for Mass Spectrometry, 2021
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Analytica Chimica Acta, 2021
Bookmarks Related papers MentionsView impact
Biochemical and Biophysical Research Communications, 1990
Phosphoinositide phospholipase C activity was investigated in human melanoma grown as solid tumor... more Phosphoinositide phospholipase C activity was investigated in human melanoma grown as solid tumor xenografts in nude mice. The enzyme was dependent on calcium for activity and was stimulated by the detergent deoxycholate. The pH optimum was 5.5 in the absence of detergent, and in the presence of deoxycholate two pH maxima were present, 5.5 and 7.2. Phospholipase C activity was inhibited by the sulfhydryl reagent dithionitrobenzoate with an IC50 in the micromolar range. Phospholipase C activity was distributed widely in mouse tissues. The enzyme showed a progressive increase in activity from heart, liver, lung, colon, spleen, to brain tissue. Mouse and human melanomas grown as solid tumors had higher phospholipase C activity than mouse brain. The relatively high activity of this enzyme in melanoma may suggest a biological role for phospholipase C in solid tumor growth.
Bookmarks Related papers MentionsView impact
Journal of Lipid Research, 2021
Bookmarks Related papers MentionsView impact
Molecular microbiology, Jan 27, 2018
Limited knowledge on the exact functions of ergostane-based sterols has hampered the application ... more Limited knowledge on the exact functions of ergostane-based sterols has hampered the application of sterol synthesis inhibitors against trypanosomatid parasites. Sterol methyltransferase (SMT) is directly involved in the synthesis of parasite specific C24-methylated sterols including ergosterol and 5-dehydroepisterol. While pharmacological studies hint at its potential as a drug target against trypanosomatids, direct evidence for the cellular function and essentiality of SMT is lacking. Here we characterized the SMT knockout mutants and their complemented strains in Leishmania major, the causative agent for cutaneous leishmaniasis. Deletion of SMT alleles led to a complete loss of C24-methylated sterols, which were replaced by cholestane-based sterols. SMT-null mutants were fully viable and replicative in culture but showed increased sensitivity to sphingolipid synthesis inhibition. They were not particularly vulnerable to heat, acidic pH, nitrosative or oxidative stress, yet exhibi...
Bookmarks Related papers MentionsView impact
Cell Reports, 2017
Bookmarks Related papers MentionsView impact
Frontiers in Bioscience, 2011
Bookmarks Related papers MentionsView impact
PLoS pathogens, 2014
Sterol biosynthesis is a crucial pathway in eukaryotes leading to the production of cholesterol i... more Sterol biosynthesis is a crucial pathway in eukaryotes leading to the production of cholesterol in animals and various C24-alkyl sterols (ergostane-based sterols) in fungi, plants, and trypanosomatid protozoa. Sterols are important membrane components and precursors for the synthesis of powerful bioactive molecules, including steroid hormones in mammals. Their functions in pathogenic protozoa are not well characterized, which limits the development of sterol synthesis inhibitors as drugs. Here we investigated the role of sterol C14α-demethylase (C14DM) in Leishmania parasites. C14DM is a cytochrome P450 enzyme and the primary target of azole drugs. In Leishmania, genetic or chemical inactivation of C14DM led to a complete loss of ergostane-based sterols and accumulation of 14-methylated sterols. Despite the drastic change in lipid composition, C14DM-null mutants (c14dm(-)) were surprisingly viable and replicative in culture. They did exhibit remarkable defects including increased me...
Bookmarks Related papers MentionsView impact
Cell Metabolism, 2015
Bookmarks Related papers MentionsView impact
The Journal of Neuroscience, 2006
It has been postulated that the development of amyloid plaques in Alzheimer's disease (AD) ma... more It has been postulated that the development of amyloid plaques in Alzheimer's disease (AD) may result from an imbalance between the generation and clearance of the amyloid-β peptide (Aβ). Although familial AD appears to be caused by Aβ overproduction, sporadic AD (the most prevalent form) may result from impairment in clearance. Recent evidence suggests that several proteases may contribute to the degradation of Aβ. Furthermore, astrocytes have recently been implicated as a potential cellular mediator of Aβ degradation. In this study, we examined the possibility that matrix metalloproteinases (MMPs), proteases known to be expressed and secreted by astrocytes, could play a role in extracellular Aβ degradation. We found that astrocytes surrounding amyloid plaques showed enhanced expression of MMP-2 and MMP-9 in aged amyloid precursor protein (APP)/presenilin 1 mice. Moreover, astrocyte-conditioned medium (ACM) degraded Aβ, lowering levels and producing several fragments after incu...
Bookmarks Related papers MentionsView impact
The EMBO Journal, 2007
Bookmarks Related papers MentionsView impact
Molecular Microbiology, 2005
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Molecular Microbiology, 2013
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Journal of Molecular and Cellular Cardiology, 2002
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Journal of Medicinal Chemistry, 1997
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Journal of Biological Chemistry, 1996
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Journal of Biological Chemistry, 1996
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Journal of Biological Chemistry, 1999
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Journal of Biological Chemistry, 2001
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Journal of Biological Chemistry, 1999
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