Pyrroloquinoline quinone and molecules mimicking its functional domains Modulators of connective tissue formation?

Hanauske-Abel, Hartmut M.; Tschank, Georg; Günzler, Volkmar; Baader, E.; Gallop, Paul M.

doi:10.1016/0014-5793(87)80062-5

Cited by 14 publications

(3 citation statements)

References 34 publications

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“…In conclusion, selective suppression of prolyl 4-hydroxylase by 2,4-PDCA may produce secondary inhibitory effects in the biosynthetic pathway of hydroxyprolyldependent proteins. Searching for potential additional effects resulting directly from the structure of that molecule, we observed that, although originally an inhibitory pilot compound deduced from the orbital interactions during the first catalytic step mediated by the intracellular prolyl 4-hydroxylase [6,8], 2,4-PDCA electronically and structurally mimics an essential part of pyrroloquinoline quinone [24], the natural compound that is the cofactor of the extracellular lysyl oxidase [25,26]. Both enzymes mediate key post-translational modifications in collagenous proteins and in elastin.…”

Section: Discussionmentioning

confidence: 99%

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Pyridinedicarboxylates, the first mechanism-derived inhibitors for prolyl 4-hydroxylase, selectively suppress cellular hydroxyprolyl biosynthesis. Decrease in interstitial collagen and Clq secretion in cell culture

Tschank¹,

Raghunath

Günzler

et al. 1987

Biochemical Journal

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Two pyridinedicarboxylates, predicted [Hanauske-Abel (1983) M.D.-Ph.D. Thesis, Philipps Universität Marburg] and later found to be potent reversible inhibitors of purified prolyl 4-hydroxylase [Majaama, Hanauske-Abel, Günzler & Kivirikko (1984) Eur. J. Biochem. 138, 239-245] were investigated with respect to their effect on hydroxyprolyl biosynthesis in the fibroblast/collagen and the macrophage/Clq systems, and the effect was compared with that of the iron chelator 2,2'-dipyridyl, the compound usually employed to inhibit cellular hydroxyprolyl formation. Only the enzyme-mechanism-derived pyridinedicarboxylates were highly selective inhibitors, and only they lacked overt cytotoxicity. Morphologically, their effect was restricted to the site of cellular hydroxyprolyl biosynthesis, i.e. the cisternae of the rough-surfaced endoplasmic reticulum. They were equally effective in the different cell types studied, and human and guinea-pig fibroblasts showed the same sensitivity. The minimal lipophilicity of the pyridinedicarboxylates necessitated high concentrations to achieve suppression of cellular hydroxyprolyl formation, but lipophilic bio-activatable pro-inhibitors may overcome this disadvantage. For the first time, experimental evidence is presented suggesting that, in cell culture, the biosynthesis of interstitial collagens and Clq can be suppressed selectively, identifying the pyridinedicarboxylates as promising pilot compounds for experiments in vivo.

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Section: Discussionmentioning

confidence: 99%

“…Both enzymes mediate key post-translational modifications in collagenous proteins and in elastin. It was suggested that pyrroloquinoline quinone-like molecules function as physiological modulators of matrix protein biosynthesis [24].…”

Section: Discussionmentioning

confidence: 99%

Pyridinedicarboxylates, the first mechanism-derived inhibitors for prolyl 4-hydroxylase, selectively suppress cellular hydroxyprolyl biosynthesis. Decrease in interstitial collagen and Clq secretion in cell culture

Tschank¹,

Raghunath

Günzler

et al. 1987

Biochemical Journal

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“…However, in addition to their antioxidant activity, some polyphenols also have the potential to promote the oxidative deamination of primary amines by oxidation to the corresponding o-quinone derivative [ 19 , 20 , 21 , 22 ]. Interestingly, through the formation of the o-quinone derivative bioflavonoids, α-aminoadipic-5-semialdehyde can form in collagen and elastin through the oxidation of the ε-amine group of lysine residues [ 20 , 23 , 24 , 25 , 26 ]. This activity has been related to non-specific chemical catalysis because it is not blocked by β-Aminopropionitrile (BAPN), a competitive inhibitor of the lysyl oxidase family [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Interplay between Polyphenols and Lysyl Oxidase Enzymes for Maintaining Extracellular Matrix Homeostasis

Añazco

Riedelsberger

Vega‐Montoto

et al. 2023

IJMS

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Collagen, the most abundant structural protein found in mammals, plays a vital role as a constituent of the extracellular matrix (ECM) that surrounds cells. Collagen fibrils are strengthened through the formation of covalent cross-links, which involve complex enzymatic and non-enzymatic reactions. Lysyl oxidase (LOX) is responsible for catalyzing the oxidative deamination of lysine and hydroxylysine residues, resulting in the production of aldehydes, allysine, and hydroxyallysine. These intermediates undergo spontaneous condensation reactions, leading to the formation of immature cross-links, which are the initial step in the development of mature covalent cross-links. Additionally, non-enzymatic glycation contributes to the formation of abnormal cross-linking in collagen fibrils. During glycation, specific lysine and arginine residues in collagen are modified by reducing sugars, leading to the creation of Advanced Glycation End-products (AGEs). These AGEs have been associated with changes in the mechanical properties of collagen fibers. Interestingly, various studies have reported that plant polyphenols possess amine oxidase-like activity and can act as potent inhibitors of protein glycation. This review article focuses on compiling the literature describing polyphenols with amine oxidase-like activity and antiglycation properties. Specifically, we explore the molecular mechanisms by which specific flavonoids impact or protect the normal collagen cross-linking process. Furthermore, we discuss how these dual activities can be harnessed to generate properly cross-linked collagen molecules, thereby promoting the stabilization of highly organized collagen fibrils.

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Therapeutic strategies for hepatic fibrosis

Chojkier

Brenner

1988

Hepatology

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Printed in U.S.A. 176 D. A. Brenner is a Pew Scholar in the Biomedical Sciences, and M. Chojkier is the recipient of a Career Research Development Award, Veterans Administration. GLOSSARY-antisense RNA: RNA that is complementary to the normally transcribed messenger RNA and is used to block the translation of messenger RNA into proteins; complementary DNA (cDNA): singie-stranded DNA complementary to a messenger RNA (i.e., the nucleotide bases of the cDNA and RNA will pair to form a duplex) and synthesized from it by in vitro reverse transcription; interkukin-1 (IL-1): a protein secreted by macrophage and other cells that has multiple effects, including cell proliferation, chemoattraction and induction of fever; phorbol esters: synthetic tumor-promoting compounds that activate protein kinase C; platelet-derived growth factor (FDGF): a protein produced by platelets and other cells that is a chemoattractant and stimulus for proliferation of mesenchymal cells; transforming growth factor @ (TGFb): a protein produced by platelets and other cells that modulates ceB development and the composition of the extracellular matrix; tumor necrosis factor alcachexin (TNFa): a protein synthesized by macrophage and other cells that has activities similar to interleukin-1 as well as inducing cachexia and cytotoxicity. Address reprint requests to: Mario Chojkier, M.D., Section of Gastroenterology,

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Pyrroloquinoline quinone and molecules mimicking its functional domains Modulators of connective tissue formation?

Cited by 14 publications

References 34 publications

Pyridinedicarboxylates, the first mechanism-derived inhibitors for prolyl 4-hydroxylase, selectively suppress cellular hydroxyprolyl biosynthesis. Decrease in interstitial collagen and Clq secretion in cell culture

Pyridinedicarboxylates, the first mechanism-derived inhibitors for prolyl 4-hydroxylase, selectively suppress cellular hydroxyprolyl biosynthesis. Decrease in interstitial collagen and Clq secretion in cell culture

Exploring the Interplay between Polyphenols and Lysyl Oxidase Enzymes for Maintaining Extracellular Matrix Homeostasis

Therapeutic strategies for hepatic fibrosis

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