Could ER Stress Be A Major Link Between Oxidative Stress And Autoimmunity In Vitiligo?

Mansuri, Mohmmad Shoab

doi:10.4172/jpd.1000123

Cited by 13 publications

(7 citation statements)

References 132 publications

(162 reference statements)

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“…Recently, the critical role of oxidative stress in vitiligo pathogenesis has been well understood 7-9. Specifically, oxidative stress leads to abnormal immunological response and melanocyte destruction, which is associated with ER stress 9, 10. However, the administration of anti-oxidative agents alone is not able to reverse the degeneration of melanocytes and induce re-pigmentation of skin in vitiligo patients 11, 12, which is probably due to the occurrence and deposits of peroxidised proteins and lipids, damaged DNA and dysfunctional mitochondria in lesional melanocytes 8, 13-15.…”

Section: Introductionmentioning

confidence: 99%

SIRT3-Dependent Mitochondrial Dynamics Remodeling Contributes to Oxidative Stress-Induced Melanocyte Degeneration in Vitiligo

Guo

Shi

et al. 2019

Theranostics

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Mitochondrial dysregulation has been implicated in oxidative stress-induced melanocyte destruction in vitiligo. However, the molecular mechanism underlying this process is merely investigated. Given the prominent role of nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase Sirtuin3 (SIRT3) in sustaining mitochondrial dynamics and homeostasis and that SIRT3 expression and activity can be influenced by oxidative stress-related signaling, we wondered whether SIRT3 could play an important role in vitiligo melanocyte degeneration by regulating mitochondrial dynamics. Methods: We initially testified SIRT3 expression and activity in normal and vitiligo melanocytes via PCR, immunoblotting and immunofluorescence assays. Then, cell apoptosis, mitochondrial function and mitochondrial dynamics after SIRT3 intervention were analyzed by flow cytometry, immunoblotting, confocal laser microscopy, transmission electron microscopy and oxphos activity assays. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), immunoblotting and immunofluorescence assays were performed to clarify the upstream regulatory mechanism of SIRT3. Finally, the effect of honokiol on protecting melanocytes and the underlying mechanism were investigated via flow cytometry and immunoblotting analysis. Results: We first found that the expression and the activity of SIRT3 were significantly impaired in vitiligo melanocytes both in vitro and in vivo . Then, SIRT3 deficiency led to more melanocyte apoptosis by inducing severe mitochondrial dysfunction and cytochrome c release to cytoplasm, with Optic atrophy 1 (OPA1)-mediated mitochondrial dynamics remodeling involved in. Moreover, potentiated carbonylation and dampened peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) activation accounted for SIRT3 dysregulation in vitiligo melanocytes. Finally, we proved that honokiol could prevent melanocyte apoptosis under oxidative stress by activating SIRT3-OPA1 axis. Conclusions: Overall, we demonstrate that SIRT3-dependent mitochondrial dynamics remodeling contributes to oxidative stress-induced melanocyte degeneration in vitiligo, and honokiol is promising in preventing oxidative stress-induced vitiligo melanocyte apoptosis.

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Section: Introductionmentioning

confidence: 99%

SIRT3-Dependent Mitochondrial Dynamics Remodeling Contributes to Oxidative Stress-Induced Melanocyte Degeneration in Vitiligo

Guo

Shi

et al. 2019

Theranostics

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“…In India, the incidence rate of vitiligo is ~0·1–8·8% . Various findings have suggested that oxidative stress may be the triggering event of melanocyte degeneration in vitiligo . Melanogenesis produces large amounts of reactive oxygen species (ROS) including H 2 O 2 , hence melanocytes are at risk of oxidative damage unless their antioxidant systems are functional .…”

mentioning

confidence: 99%

The catalase gene promoter and 5ʹ-untranslated region variants lead to altered gene expression and enzyme activity in vitiligo

et al. 2017

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“…PARP‐1 and related PARP family members are at the intersection of conversing stress signalling pathways. Oxidative stress causes disruption in redox potential that extends to the ER, causing accumulation of misfolded proteins, finally stimulating the unfolded protein response (UPR) . It would be interesting to know if PARP‐1 has a role in ER stress‐mediated cell death as it is upstream to autophagy, where PARP‐1 is demonstrated to play an essential role.…”

Section: Parp‐1: Structure Activation Signals and Its Diverse Cellulmentioning

confidence: 99%

The PARP family: insights into functional aspects of poly (ADP‐ribose) polymerase‐1 in cell growth and survival

et al. 2016

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PARP family members can be found spread across all domains and continue to be essential molecules from lower to higher eukaryotes. Poly (ADP-ribose) polymerase 1 (PARP-1), newly termed ADP-ribosyltransferase D-type 1 (ARTD1), is a ubiquitously expressed ADP-ribosyltransferase (ART) enzyme involved in key cellular processes such as DNA repair and cell death. This review assesses current developments in PARP-1 biology and activation signals for PARP-1, other than conventional DNA damage activation. Moreover, many essential functions of PARP-1 still remain elusive. PARP-1 is found to be involved in a myriad of cellular events via conservation of genomic integrity, chromatin dynamics and transcriptional regulation. This article briefly focuses on its other equally important overlooked functions during growth, metabolic regulation, spermatogenesis, embryogenesis, epigenetics and differentiation. Understanding the role of PARP-1, its multidimensional regulatory mechanisms in the cell and its dysregulation resulting in diseased states, will help in harnessing its true therapeutic potential.

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Could ER Stress Be A Major Link Between Oxidative Stress And Autoimmunity In Vitiligo?

Cited by 13 publications

References 132 publications

SIRT3-Dependent Mitochondrial Dynamics Remodeling Contributes to Oxidative Stress-Induced Melanocyte Degeneration in Vitiligo

SIRT3-Dependent Mitochondrial Dynamics Remodeling Contributes to Oxidative Stress-Induced Melanocyte Degeneration in Vitiligo

The catalase gene promoter and 5ʹ-untranslated region variants lead to altered gene expression and enzyme activity in vitiligo

The PARP family: insights into functional aspects of poly (ADP‐ribose) polymerase‐1 in cell growth and survival

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