Isolation and Identification of Intermediates of the Oxidative Bilirubin Degradation

Ritter, Marcel; Seidel, Raphael A.; Bellstedt, Peter; Schneider, Bernd; Bauer, Michael; Görls, Helmar; Pohnert, Georg

doi:10.1021/acs.orglett.6b02287

Cited by 19 publications

(50 citation statements)

References 17 publications

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“…Several structures are shared with heme degradation products. We unambiguously identified PDPs B1, and B2 as well as BOX C by comparison with authentic standards (Scheme ) . These metabolites were quantified in amounts in the pg mg −1 dry mass range (Figure ).…”

Section: Resultsmentioning

confidence: 91%

“…To identify pyrrolic and dipyrrolic Chl degradation products, we initially performed a model oxidation in vitro. We used a procedure established for the investigation of heme degradation to address the lower molecular weight fraction of Chl degradation products . Chl a , suspended in sodium hydroxide solution, was neutralized with hydrogen chloride before oxidation with hydrogen peroxide.…”

Section: Resultsmentioning

confidence: 99%

“…To avoid this, sodium hydroxide in methanol was used with 10 % hydrogen peroxide, which resulted in higher amounts of degradation products. With this optimized method, we could prove by UHPLC/HR‐MS and the addition of standards the occurrence of PDP B1/B2 as well as of BOX A, B, C and hematinic acid (HA) as degradation products of Chl a in vitro (Scheme , see Supporting Information, Figures S7–S12). The finding of BOX A seems surprising, considering that the corresponding part of Chl holds an ethyl instead of a vinyl group.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, two isomers in each structural group are observed (1 for OH at vinyl pyrrole and 2 for OH at propionic acid pyrrole). Both isomers of each group are in an equilibrium and are proven intermediates to BOXes . Those oxidative heme degradation products were quantified in nano‐ to micromolar concentrations with a 20–80 times higher abundance for PDPs compared to BOXes in bile, gallstones and the cerebrospinal fluid of stroke patients .…”

Section: Introductionmentioning

confidence: 99%

“…Both isomers of each group are in an equilibrium and are proven intermediates to BOXes . Those oxidative heme degradation products were quantified in nano‐ to micromolar concentrations with a 20–80 times higher abundance for PDPs compared to BOXes in bile, gallstones and the cerebrospinal fluid of stroke patients . Heme degradation products are involved in vessel constrictions as stroke complication and act as effectors in the liver …”

Section: Introductionmentioning

confidence: 99%

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Pyrrolic and Dipyrrolic Chlorophyll Degradation Products in Plants and Herbivores

Ritter

Oetama

Schulze

et al. 2020

Chemistry A European J

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The degradation of chlorophyll,t he omnipresent green pigment, has been investigatedi ntensively over the last 30 years resulting in manye lucidated tetrapyrrolic degradationp roducts. With ac omparison to the degradation of the structurally similarh eme, we hereby propose an ovel additionalc hlorophyll degradation mechanism to mono-and dipyrrolic products.T his is the first proof of the occurrence of af amilyo fm ono-and dipyrrols in leaves that are previously only known as heme degradationp roducts.T his prod-uct familyi sa lso found in spit and feces of herbivores with specific metabolomic patterns reflecting the origin of the samples. Based on chromatographica nd mass spectrometric evidencea swell as on mechanistic considerations we also suggest severalt entative new degradation products.O ne of them,d ihydro BOX A, was fully confirmed as an ovel natural product by synthesis andc omparison of its spectroscopic data.Supporting information and the ORCID identification number(s) for the author(s) of this articlecan be found under: https://doi.org/10. Scheme1.Enzymatic chlorophyll degradation in plants.Scheme2.Enzymatic (top) andoxidativeheme degradation by reactive oxygen species (ROS) to PDPs and BOXes.

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Section: Resultsmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Pyrrolic and Dipyrrolic Chlorophyll Degradation Products in Plants and Herbivores

Ritter

Oetama

Schulze

et al. 2020

Chemistry A European J

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Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

Yang

et al. 2019

Adv Funct Materials

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Although nanoparticles are expected to revolutionize cancer treatment, their low efficacy remains the greatest limiting factor. Recent investigations found that nanoparticles' golden principle, the enhanced permeability and retention (EPR) effect, is limited by the complicated tumor microenvironment. Herein, novel transformable nanomaterials are designed to utilize the EPR effect more effectively. By tandem conjugation of the hydrophobic head (chlorin e6 (Ce6) or bilirubin (BR)), peptide to form hydrogen bond (Phe-Phe-Val-Leu-Lys (FFVLK)), and hydrophilic tail (polyethylene glycol (PEG)), chimeric molecules that can form micelles (Ce6/BR-FFVLK-PEG) in aqueous solution are synthesized. Notably, the spherical micelles retain shape transformability. After circulation and distribution, they respond to 650 nm laser irradiation, and morphologically change into nanofibers so as to facilitate their retention markedly inside the tumor. Upon loading a reactive oxygen species-responsive paclitaxel dimer with thioketal linker (PTX 2 -TK), the resultant PTX 2 -TK@Ce6/BR-FFVLK-PEG nanomedicine serves as a potent chemo-photodynamic therapeutic for cancer treatment. Evaluations at both cell level and animal level reveal that PTX 2 -TK@Ce6/BR-FFVLK-PEG exhibits superior biocompatibility and biodistribution, and suppresses 82.6% of in vitro cell growth and 61.8% of in vivo tumor growth at a common dose of intravenous injection (10 mg kg −1 PTX and 3.3 mg kg −1 Ce6), becoming a novel nanomedicine with extraordinary potential in cancer therapy.

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All Three Supersystems—Nervous, Vascular, and Immune—Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage

Dreier,

Joerk,

Uchikawa

et al. 2024

Transl. Stroke Res.

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The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical infarcts are caused by acute severe vasospastic events, so-called spreading ischemia, triggered by spontaneously occurring spreading depolarization. In locations where a spreading depolarization passes through, cerebral blood flow can drastically drop within a few seconds and remain suppressed for minutes or even hours, often followed by high-amplitude, sustained hyperemia. In spreading depolarization, neurons lead the event, and the other cells of the neurovascular unit (endothelium, vascular smooth muscle, pericytes, astrocytes, microglia, oligodendrocytes) follow. However, dysregulation in cells of all three supersystems—nervous, vascular, and immune—is very likely involved in the dysfunction of the neurovascular unit underlying spreading ischemia. It is assumed that subarachnoid blood, which lies directly on the cortex and enters the parenchyma via glymphatic channels, triggers these dysregulations. This review discusses the neuroglial, neurovascular, and neuroimmunological dysregulations in the context of spreading depolarization and spreading ischemia as critical elements in the pathogenesis of cortical infarcts after subarachnoid hemorrhage.

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Isolation and Identification of Intermediates of the Oxidative Bilirubin Degradation

Cited by 19 publications

References 17 publications

Pyrrolic and Dipyrrolic Chlorophyll Degradation Products in Plants and Herbivores

Pyrrolic and Dipyrrolic Chlorophyll Degradation Products in Plants and Herbivores

Linear Chimeric Triblock Molecules Self‐Assembled Micelles with Controllably Transformable Property to Enhance Tumor Retention for Chemo‐Photodynamic Therapy of Breast Cancer

All Three Supersystems—Nervous, Vascular, and Immune—Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage

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