A cell culture study on melanocytes from patients with neurofibromatosis-1

Kaufmann, Dieter; Krone, W.; Hochsattel, R; Martin, Renate

doi:10.1007/bf00510091

Cited by 22 publications

(14 citation statements)

References 17 publications

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“…In NF1 patients, it has been shown that their CALMs have an increased number of melanocytes, although there is still some debate on this issue36. Others have demonstrated at the organelle level an even greater concentration of melanin and macromelanosomes in both CALM and non-CALM skin when compared to non-NF1 skin controls37. Recent investigations have found that the melanocyte in the CALM has a mutation in both copies of the NF1 gene and that the melanocytes of non-CALM NF1 skin show the germline mutation only22.…”

Section: Cutaneous Manifestationsmentioning

confidence: 99%

Neurofibromatosis type 1

Boyd¹,

Korf²,

Theos³

2009

Journal of the American Academy of Dermatology

441

365

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Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder affecting approximately 1 in 3500 people. Significant advances in the understanding of the pathophysiology of NF1 have been made in the last decade. While no medical therapies are currently available, trials are ongoing to discover and test medical treatments for the various manifestations of NF1, primarily plexiform neurofibromas, learning disabilities, and optic pathway gliomas. Additionally, mutational analysis has become available on a clinical basis and is useful for diagnostic confirmation in individuals who do not fulfill diagnostic criteria or when prenatal diagnosis is desired. There are several disorders which may share overlapping features with NF1; in 2007, a disorder with cutaneous findings similar to NF1 was described. This paper addresses the dermatologist's role in diagnosis and management of NF1 and describes the variety of cutaneous and extracutaneous findings in NF1 to which the dermatologist may be exposed.

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Section: Cutaneous Manifestationsmentioning

confidence: 99%

Neurofibromatosis type 1

Boyd¹,

Korf²,

Theos³

2009

Journal of the American Academy of Dermatology

441

365

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“…The sharply contrasted brown particles of 3-8 gm diameter mostly found at the periphery of the cells were used for the determination of the number of LMC (Kaufmann et al 1989(Kaufmann et al , 1990. Cultures were set up at a cell density of 10000 per cm 2.…”

Section: Determination Of the Number Of Large Melanosome Complexesmentioning

confidence: 99%

“…Indeed, the composition of the epidermal melanin unit is shifted in favor of the melanocytes even in the normally pigmented skin of NF 1 patients and more so in the dark brown card au lait macules (Frenk and Marazzi 1984;Ishida 1987). It has been shown that NF 1 melanocytes in culture produce increased amounts of large melanosome complexes (LMC) (Kaufmann et al 1989(Kaufmann et al , 1990, putative precursors of the well-known melanin macroglobules (MMG) (Nakagawa et al 1984), which are also more abundant in vivo in melanocytes of normally pigmented skin of NF 1 patients than in those of healthy donors (Martuza et al 1985). Cultured card au lait macules show higher scores of LMC, and melanocytes in caf6 au lait macules contain higher amounts of MMG than those from the normally pigmented skin of the same patient.…”

Section: Introductionmentioning

confidence: 99%

Increased melanogenesis in cultured epidermal melanocytes from patients with neurofibromatosis 1 (NF1)

et al. 1991

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Melanocyte cultures from the normally pigmented skin of patients with neurofibromatosis 1 (NF 1) have a higher melanin content than those from the skin of healthy donors. An additional increase in the amount of melanin per cell was found in 5 out of 6 lines of melanocytes derived from café au lait macules of NF 1 patients. Omission of the tumor promoter phorbol-12-myristate-13-acetate from the culture medium brings about a comparable increase in the melanin content in all three kinds of melanocyte cultures. Cultures of NF 1 melanocytes show a higher tyrosine hydroxylase activity than those of control melanocytes, and incorporate larger amounts of dihydroxyphenylalanine than the latter. We conclude that melanogenesis in epidermis melanocytes is affected by defective alleles of the NF 1 gene. Our findings do not contradict the hypothesis that the defect underlying NF 1 impairs the inhibition of a wild-type RAS oncogene by interfering with the GTPase-activating function of the NF 1 gene product.

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“…Likewise, the omission of PMA decreases the neurofibromin content and increases the amount of melanin drastically, as shown already in melanocytes from other controls and NF1 patients (Kaufmann et al, 1989(Kaufmann et al, , 1991. If the excess of neurofibromin in the chloroquine-treated melanocytes correlates with an increased neurofibromin activity then the increase of melanin should not appear.…”

Section: The Higher Neurofibromin Content Upon Incubation With Chloromentioning

confidence: 75%

“…It was shown earlier in vivo and in vitro that neurofibromin is able to influence the regulation of melanogenesis (Martuza et al, 1985;Kaufmann et al, 1989Kaufmann et al, , 1991.…”

Section: Discussionmentioning

confidence: 98%

On the Lysosomal Degradation of Neurofibromin and Its Phosphorylation in Cultured Melanocytes

Kaufmann

Junge²,

Bartelt³

et al. 1999

Biological Chemistry

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Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders in humans. Most of the NF1 gene mutations result in a reduction of the amount of neurofibromin to about 50%. Recently, we found that the level of neurofibromin can be regulated post-translationally through the alteration of its half-life. Here, we investigated whether lysosomes are involved in this post-translational regulation in cultured melanocytes of NF1 patients and controls. When the lysosomal degradation was inhibited by chloroquine, an increase of neurofibromin by a factor of 2 to 3, correlating with an increased half-life, was measured. Incubation with phosphoprotein-phosphatase inhibitors also increased the neurofibromin content in melanocytes. Investigations on phosphorylation of neurofibromin revealed a basal phosphorylation in melanocytes cultured with growth factor-deprived medium that increased upon incubation with the growth stimulators PMA or bFGF. Because both factors are also able to increase the half-life of neurofibromin, we suggest its phosphorylation to be an important step in protecting neurofibromin against specific lysosomal degradation.

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A cell culture study on melanocytes from patients with neurofibromatosis-1

Cited by 22 publications

References 17 publications

Neurofibromatosis type 1

Neurofibromatosis type 1

Increased melanogenesis in cultured epidermal melanocytes from patients with neurofibromatosis 1 (NF1)

On the Lysosomal Degradation of Neurofibromin and Its Phosphorylation in Cultured Melanocytes

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