A Novel Perspective on the Biology of Bilirubin in Health and Disease

Gazzin, Silvia; Vı́tek, Libor; Watchko, Jon F.; Shapiro, Steven M.; Tiribelli, Claudio

doi:10.1016/j.molmed.2016.07.004

Cited by 150 publications

(140 citation statements)

References 71 publications

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“…Bilirubin is receiving increasing attention for its powerful antioxidant activity, already recognized in vitro 34 but now well demonstrated in vivo , especially in the cardiovascular system 35 . Indeed, a mild increase of plasma bilirubin improves endothelial function preventing or reducing the severity of cardiovascular pathologies 36 and metabolic diseases 37 and, also, is protective against neuronal death induced by ischemia/reperfusion 38 .…”

Section: Discussionmentioning

confidence: 99%

Differentiation impairs Bach1 dependent HO-1 activation and increases sensitivity to oxidative stress in SH-SY5Y neuroblastoma cells

Piras

Furfaro

Brondolo

et al. 2017

Sci Rep

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Neuronal adaptation to oxidative stress is crucially important in order to prevent degenerative diseases. The role played by the Nrf2/HO-1 system in favoring cell survival of neuroblastoma (NB) cells exposed to hydrogen peroxide (H2O2) has been investigated using undifferentiated or all-trans retinoic acid (ATRA) differentiated SH-SY5Y cells. While undifferentiated cells were basically resistant to the oxidative stimulus, ATRA treatment progressively decreased cell viability in response to H2O2. HO-1 silencing decreased undifferentiated cell viability when exposed to H2O2, proving the role of HO-1 in cell survival. Conversely, ATRA differentiated cells exposed to H2O2 showed a significantly lower induction of HO-1, and only the supplementation with low doses of bilirubin (0,5–1 μM) restored viability. Moreover, the nuclear level of Bach1, repressor of HO-1 transcription, strongly decreased in undifferentiated cells exposed to oxidative stress, while did not change in ATRA differentiated cells. Furthermore, Bach1 was displaced from HO-1 promoter in undifferentiated cells exposed to H2O2, enabling the binding of Nrf2. On the contrary, in ATRA differentiated cells treated with H2O2, Bach1 displacement was impaired, preventing Nrf2 binding and limiting HO-1 transcription. In conclusion, our findings highlight the central role of Bach1 in HO-1-dependent neuronal response to oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Differentiation impairs Bach1 dependent HO-1 activation and increases sensitivity to oxidative stress in SH-SY5Y neuroblastoma cells

Piras

Furfaro

Brondolo

et al. 2017

Sci Rep

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“…Bilirubin has been regarded as a marker of hepatobiliary and hematological disorders for a long time . However, recent studies have demonstrated that bilirubin also plays a role in antioxidation, inflammation, and cancer . An inverse association between bilirubin and cancer risk has been uncovered in non‐small‐cell lung cancer, breast cancer, and colorectal cancer .…”

Section: Introductionmentioning

confidence: 99%

Serum bilirubin level predicts postoperative overall survival in oral squamous cell carcinoma

Zhang

Zhu

et al. 2018

J Oral Pathology Medicine

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“…Interestingly, some degradation products of heme are known to possess a cytoprotective function; by decreasing oxidative stress, slightly elevated levels of bilirubin (BR) can aid in the prevention of a variety of diseases and are associated with longer telomeres . Also cancer related activities are known for the bile pigments; unconjugated BR was shown to induce apoptosis in colon cancer cells, and biliverdin has recently been recognized for its potential as anti‐cancer agent via inhibition of proliferation and angiogenesis .…”

Section: Beyond Chlorophyll Detoxification – Potential Bioactivities mentioning

confidence: 99%

In Search of Bioactivity – Phyllobilins, an Unexplored Class of Abundant Heterocyclic Plant Metabolites from Breakdown of Chlorophyll

Moser

Kräutler

2019

Israel Journal of Chemistry

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The fate of the green plant pigment chlorophyll (Chl) in de‐greening leaves has long been a fascinating biological puzzle. In the course of the last three decades, various bilin‐type products of Chl breakdown have been identified, named phyllobilins (PBs). Considered ‘mere’ leftovers of a controlled biological Chl detoxification originally, the quest for finding relevant bioactivities of the PBs has become a new paradigm. Indeed, the PBs are abundant in senescent leaves, in ripe fruit and in some vegetables, and they display an exciting array of diverse heterocyclic structures. This review outlines briefly which types of Chl breakdown products occur in higher plants, describes basics of their bio‐relevant structural and chemical properties and gives suggestions as to ‘why’ the plants produce vast amounts of uniquely ‘decorated’ heterocyclic compounds. Clearly, it is worthwhile to consider crucial metabolic roles of PBs in plants, which may have practical consequences in agriculture and horticulture. However, PBs are also part of our plant‐based nutrition and their physiological and pharmacological effects in humans are of interest, as well.

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A Novel Perspective on the Biology of Bilirubin in Health and Disease

Cited by 150 publications

References 71 publications

Differentiation impairs Bach1 dependent HO-1 activation and increases sensitivity to oxidative stress in SH-SY5Y neuroblastoma cells

Differentiation impairs Bach1 dependent HO-1 activation and increases sensitivity to oxidative stress in SH-SY5Y neuroblastoma cells

Serum bilirubin level predicts postoperative overall survival in oral squamous cell carcinoma

In Search of Bioactivity – Phyllobilins, an Unexplored Class of Abundant Heterocyclic Plant Metabolites from Breakdown of Chlorophyll

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