A Role for Tyrosinase-Related Protein 1 in 4-tert-Butylphenol-Induced Toxicity in Melanocytes

Abstract

Vitiligo presents with depigmented cutaneous lesions following localized melanocyte death. Multiple factors contribute to cell death, including genetically determined susceptibility to trauma, and environmental factors, such as exposure to 4-tert-butylphenol (4-TBP). We demonstrate that 4-TBP induces oxidative stress that is more readily overcome by melanocytes from normally pigmented individuals than from two individuals with vitiligo. The antioxidant catalase selectively and significantly reduced death of melanocytes derived from two individuals with vitiligo, indicating a role for oxidative stress in vitiligo pathogenesis. In normal melanocytes, oxidative stress results in reduced expression of microphthalmia-associated transcription factor (MITF). Melanocyte-stimulating hormone-induced expression of MITF protein caused increased sensitivity to 4-TBP, whereas sensitivity of melanomas correlated with MITF expression. MITF stimulates melanin synthesis by up-regulating expression of melanogenic enzymes such as tyrosinase-related protein-1 (Tyrp1). Although melanin content per se did not affect sensitivity to 4-TBP, expression of Tyrp1 significantly increased sensitivity. Melanocytes and melanomas that express functional Tyrp1 were significantly more sensitive to 4-TBP than Tyrp1-null cells. Thus, normal melanocytes respond to 4-TBP by reducing expression of MITF and Tyrp1. We hypothesize that melanocytes in vitiligo demonstrate reduced ability to withstand oxidative stress due, partly, to a disruption in

Isolation and Characterization of 4- tert -Butylphenol-Utilizing Sphingobium fuliginis Strains from Phragmites australis Rhizosphere Sediment

“…4-tert-Butylphenol is widely distributed in aquatic environments, including river waters (20), seawaters (17), river sediments (17), marine sediments (23), and effluent samples from sewage treatment plants and wastewater treatment plants (22). Furthermore, 4-tert-butylphenol interacts with estrogen receptors (29,30,34,35,39) and exhibits other toxic effects on aquatic organisms and humans (4,15,16,25,26,42,43). Therefore, it is necessary to study the biodegradation of 4-tert-butylphenol to understand its fate in the aquatic environment, to establish technologies to treat the waters polluted by it, and to remove it from contaminated environments.…”

DermaGene and VitmiRS: a comprehensive systems analysis of genetic dermatological disorders

“…TYRP1 is targeted by hsa-miR-577, and its reduced expression as induced by miR-577 leads to increased sensitivity of melanocytes to oxidative stress causing early cell death of vitiligo melanocytes (Manga et al 2006;Sturm and Duffy 2012). Also, the downregulation of PTPN22 was observed to be influenced by miR-577 which triggers the overexpression of T cells and suppresses antiapoptotic AKT kinase inducing melanocyte destruction, thereby, rendering susceptibility to autoimmunity in vitiligo patients (Mansuri et al, 2016).…”

Stimulating effect of modified Goa-Gi-Um herbal remedy on melanogenesis in B16F10 melanoma cells

“…그러므로 근본적인 치료는 하지 못 하더라도 백반증의 증세를 완화시키는 방법으로 피부세포에서 멜라닌 합성을 증가시키는 것이 필요하다. 멜라닌은 멜라닌 생성세포 (melanocytes)로부터 합성되고 자외선조사나 독성 물질과 화학물질을 흡수함으로써 피부를 보호하는데 중요한 역할을 한다 2,5,6) . 그러므로 멜라닌 합성이 정상적으로 일어나 지 않는 사람들에서는 모든 피부가 백색으로 되기보다는 부분 적으로 백색으로 변해 얼룩이 생기는 외형적인 문제점도 있고 외부 자극에 민감해지는 것이 더 문제이다.…”

“…TRP-1은 dihydroxy indole carboxylic acid oxidase로서 5,6-dihydroxyindole-2-carboxylic acid (DHICA)를 indol-5,6-quinone-2-carboxylic acid로 산 화시키는 효소이고, TRP-1은 tyrosinase를 안정화시키고 tyrosinase의 활성을 조절하는 역할을 한다. TRP-2는 DOPA Chrome tautomerase로써 DOPA chrome을 DHICA로 변화시켜 멜라닌세포를 이루는 eumelanon과 pheomelanon 을 형성하고 이들의 비율에 따라 피부, 머리타락, 눈동자의 색깔 등이 결정된다 5,6) . 멜라닌 합성은 자외선 조사와 α-melanocyte stimulating hormone (MSH)로 인해 활성화된다 6) .…”

“…TRP-2는 DOPA Chrome tautomerase로써 DOPA chrome을 DHICA로 변화시켜 멜라닌세포를 이루는 eumelanon과 pheomelanon 을 형성하고 이들의 비율에 따라 피부, 머리타락, 눈동자의 색깔 등이 결정된다 5,6) . 멜라닌 합성은 자외선 조사와 α-melanocyte stimulating hormone (MSH)로 인해 활성화된다 6) . Fig.…”