Increased levels of mitochondrial DNA copy number in patients with vitiligo

Vaseghi, Hajar; Houshmand, Massoud; Jadali, Zohreh

doi:10.1111/ced.13185

Cited by 29 publications

(22 citation statements)

References 22 publications

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“…IL-8 is known to induce the chemotaxis for neutrophils; however, the migration of neutrophils depends not only on the chemotactic function of IL-8 but also on the polarity of neutrophils, which is mediated by Rho GTPases (Pantarelli and Welch, 2018). Recently, some studies have found that 8-hydroxydeoxyguanosine, an oxidative stresseinduced DNA product that is elevated in vitiligo (Vaseghi et al, 2017;Wei et al, 2013), could inhibit the function of Rho GTPases (Park et al, 2017). Therefore, oxidative stress may inhibit the migratory ability of neutrophils and thus suppress the cutaneous infiltration of neutrophils in vitiligo, even though the level of IL-8 is elevated in the disease.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress–Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo

Cui

Zhang

et al. 2019

Journal of Investigative Dermatology

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Vitiligo is a cutaneous depigmentation disorder caused by the destruction of epidermal melanocytes. The generation and the skin infiltration of autoreactive CD8 þ cytotoxic T cells triggered by oxidative stress play a critical role in vitiligo. High-mobility group protein B1 (HMGB1) is a classic damage-associated molecular pattern molecule with strong proinflammatory effects in inflammatory reactions. A previous study reported an enhanced expression of HMGB1 in vitiligo lesions, but the role of HMGB1 in cutaneous inflammation of vitiligo is still unknown. In the present study, we initially found that HMGB1 was released from the nucleus of melanocytes in vitiligo perilesional skin. Furthermore, cultured normal human melanocytes could release HMGB1 under treatment with hydrogen peroxide. Moreover, HMGB1 facilitated the secretion of CXCL16 and IL-8 from keratinocytes by binding to the receptor for advanced glycation end products and activating NF-kB and extracellular signaleregulated kinase signaling pathways. Subsequently, HMGB1 led to the formation of chemotaxis for the migration of CD8 þ T cells from patients with vitiligo by increasing the release of CXCL16 from keratinocytes. Additionally, HMGB1 promoted the maturation of dendritic cells from patients with vitiligo. Altogether, our study demonstrates that HMGB1 released from melanocytes contributes to the formation of oxidative stresseinduced autoimmunity in vitiligo.

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Section: Discussionmentioning

confidence: 99%

Oxidative Stress–Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo

Cui

Zhang

et al. 2019

Journal of Investigative Dermatology

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“…Mitochondria are the primary source of intracellular ROS, a group of chemically reactive molecules containing oxygen, hydroxyl radical (•OH), superoxide anion (O 2 -), singlet oxygen (O₂) and hydrogen peroxide (H 2 O 2 ), as side-products of the mitochondrial electron transport chain reaction during cellular respiration [4]. ROS play important roles in cell signalling pathways such as growth, differentiation, metabolism and apoptosis [4,5]. They are also regarded as a double-edged sword in cancer cells since low doses of ROS can promote cell proliferation and invasion, whereas excessive levels of ROS cause oxidative damage to proteins, lipids, RNA and DNA which consequently induce cell death [6,7].…”

Section: Introductionmentioning

confidence: 99%

ROS as a Novel Indicator to Predict Anticancer Drug Efficacy

Zaidieh

Smith

Ball

et al. 2019

Preprint

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Background Mitochondria are considered a primary intracellular site of reactive oxygen species (ROS) generation. Generally, cancer cells with mitochondrial genetic abnormalities (copy number change and mutations) have escalated ROS levels compared to normal cells. Since high levels of ROS can trigger apoptosis, treating cancer cells with low doses of mitochondria-targeting / ROS-stimulating agents may offer cancer-specific therapy. This study aimed to investigate how baseline ROS levels might influence cancer cells’ response to ROS-stimulating therapy. Methods Four cancer and one normal cell lines were treated with a conventional drug (cisplatin) and a mitochondria-targeting agent (dequalinium chloride hydrate) separately and jointly. Cell viability was assessed and drug combination synergisms were indicated by the combination index (CI). Mitochondrial DNA copy number (MtDNAcn), ROS and mitochondrial membrane potential (MMP) were measured, and the relative expression levels of the genes and proteins involved in ROS-mediated apoptosis pathways were also investigated. Results Our data showed a correlation between the baseline ROS level, mtDNAcn and drug sensitivity in the tested cells. Synergistic effect of both drugs was also observed with ROS being the key contributor in cell death. Conclusions Our findings suggest that mitochondria-targeting therapy could be more effective compared to conventional treatments. In addition, cancer cells with low levels of ROS may be more sensitive to the treatment, while cells with high levels of ROS may be more resistant. Doubtlessly, further studies employing a wider range of cell lines and in vivo experiments are needed to validate our results. However, this study provides an insight into understanding the influence of intracellular ROS on drug sensitivity, and may lead to the development of new therapeutic strategies to improve efficacy of anticancer therapy.

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“…The mitochondrial electron transport chain was proposed as the main intracellular site of ROS over‐production in vitiligo patients. Interestingly, increased mitochondrial DNA copy number and its ROS‐triggered oxidation was found in the blood of vitiligo patients (Vaseghi, Houshmand, & Jadali, ) confirming the role of mitochondria in vitiligo pathogenesis.…”

Section: Theories About Melanocytes Destruction and Oxidative Stress mentioning

confidence: 82%

Functional nutrition as integrated approach in vitiligo management

Nardo

Barygina

França

et al. 2018

Dermatologic Therapy

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Vitiligo is a common disease of unknown cause that produces disfiguring white patches of depigmentation that can be treated using various new and experimental therapies, such as narrow-band ultraviolet B (NB-UVB) microphototherapy, NB-UVB excimer laser, and monochromatic excimer light. Medical treatments include topical corticosteroids and other topical treatments, such as antioxidants, tacrolimus and pimecrolimus, prostaglandin E, and vitamin D derivatives (Lotti, Berti, & Moretti, ). The goal of treating vitiligo is to make it less noticeable either by restoring lost pigment or by eliminating remaining pigment. Functional foods and healthy diet, with nutrients, form a variety of sources, could be considered an integral part, as well as helpful, of vitiligo's medical therapy.

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Increased levels of mitochondrial DNA copy number in patients with vitiligo

Abstract: These data suggest that increase in mtDNAcn and oxidative DNA damage may be involved in the pathogenesis of vitiligo.

Cited by 29 publications

References 22 publications

Oxidative Stress–Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo

Oxidative Stress–Induced HMGB1 Release from Melanocytes: A Paracrine Mechanism Underlying the Cutaneous Inflammation in Vitiligo

ROS as a Novel Indicator to Predict Anticancer Drug Efficacy

Functional nutrition as integrated approach in vitiligo management

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