ACTH STIMULATES MELANOGENESIS IN CULTURED HUMAN MELANOCYTES

1994 ◽  
Vol 140 (1) ◽  
pp. R1-R3 ◽  
Author(s):  
G. Hunt ◽  
C. Todd ◽  
S. Kyne ◽  
A.J. Thody
Keyword(s):  
Dose Response ◽  
Plasma Levels ◽  
Culture System ◽  
Skin Pigmentation ◽  
Physiological Role ◽  
Melanin Content ◽  
Response Curves ◽  
Human Melanocytes ◽  
First Time ◽  
Rate Limiting

ABSTRACT While ACTH is known to induce skin pigmentation in man, its effects on cultured human melanocytes have not been investigated. Using a culture system free of artificial mitogens, we report for the first time that ACTH stimulates melanogenesis in cultured human melanocytes. While ACTH, α-MSH and the synthetic α-MSH analogue Nle4DPhe7α-MSH all stimulate the activity of tyrosinase, the rate limiting enzyme in melanogenesis, and all produce a 50% increase in the melanin content of the cells at a concentration of 10−8-10−7 mol/l, the shapes of the dose response curves differ: those for the MSH peptides are sigmoidal while those for ACTH are biphasic. In addition, human melanocytes are able to respond to concentrations of ACTH comparable with physiological plasma levels. We suggest that ACTH may be relatively more important than α-MSH as a pigmentary hormone in man and could have a physiological role in skin pigmentation.

scholarly journals Mammalian pigmentation is regulated by a distinct cAMP-dependent mechanism that controls melanosome pH

2018 ◽  
Vol 11 (555) ◽  
pp. eaau7987 ◽  
Author(s):  
Dalee Zhou ◽  
Koji Ota ◽  
Charlee Nardin ◽  
Michelle Feldman ◽  
Adam Widman ◽  
...  
Keyword(s):  
Skin Cancer ◽  
Skin Color ◽  
Skin Pigmentation ◽  
Melanin Production ◽  
Melanocortin 1 Receptor ◽  
New Class ◽  
Camp Pathway ◽  
Human Melanocytes ◽  
Rate Limiting

The production of melanin increases skin pigmentation and reduces the risk of skin cancer. Melanin production depends on the pH of melanosomes, which are more acidic in lighter-skinned than in darker-skinned people. We showed that inhibition of soluble adenylyl cyclase (sAC) controlled pigmentation by increasing the pH of melanosomes both in cells and in vivo. Distinct from the canonical melanocortin 1 receptor (MC1R)–dependent cAMP pathway that controls pigmentation by altering gene expression, we found that inhibition of sAC increased pigmentation by increasing the activity of tyrosinase, the rate-limiting enzyme in melanin synthesis, which is more active at basic pH. We demonstrated that the effect of sAC activity on pH and melanin production in human melanocytes depended on the skin color of the donor. Last, we identified sAC inhibitors as a new class of drugs that increase melanosome pH and pigmentation in vivo, suggesting that pharmacologic inhibition of this pathway may affect skin cancer risk or pigmentation conditions.

scholarly journals Ginsenosides Rb1 and Rg1 Stimulate Melanogenesis in Human Epidermal Melanocytes via PKA/CREB/MITF Signaling

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Mao Lin ◽  
Bao-Xiang Zhang ◽  
Ci Zhang ◽  
Nan Shen ◽  
Yun-Ying Zhang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Skin Pigmentation ◽  
Camp Response Element Binding ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Melanin Content ◽  
Protein Levels ◽  
Human Melanocytes ◽  
Element Binding Protein ◽  
Phosphorylated Creb

Reduced or defective melanin skin pigmentation may cause many hypopigmentation disorders and increase the risk of damage to the skin triggered by UV irradiation. Ginsenosides Rb1 and Rg1 have many molecular targets including the cAMP-response element-binding protein (CREB), which is involved in melanogenesis. This study aimed to investigate the effects of ginsenosides Rb1 and Rg1 on melanogenesis in human melanocytes and their related mechanisms. The effects of Rb1 and Rg1 on cell viability, tyrosinase activity, cellular melanin content and protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and activation of CREB in melanocytes were assessed. Results showed that Rb1 or Rg1 significantly increased cellular melanin content and tyrosinase activity in a dose-dependent manner. By contrast, the cell viability of melanocytes remained unchanged. After exposure to Rb1 or Rg1, the protein levels of tyrosinase, MITF, and phosphorylated CREB were significantly increased. Furthermore, pretreatment with the selective PKA inhibitor H-89 significantly blocked the Rb1- or Rg1-induced increase of melanin content. These findings indicated that Rb1 and Rg1 increased melanogenesis and tyrosinase activity in human melanocytes, which was associated with activation of PKA/CREB/MITF signaling. The effects and mechanisms of Rb1 or Rg1 on skin pigmentation deserve further study.

scholarly journals Halotolerance (ionic NaCl) and chaotolerance (ionic MgCl2) of the human pathogen Wallemia mellicola isolated, for the first time, from indoor air in Poland

2018 ◽  
Vol 53 (1) ◽  
Author(s):  
Andrzej Chlebicki ◽  
Wojciech Spisak ◽  
Marta Saługa
Keyword(s):  
Indoor Air ◽  
Dose Response ◽  
Aureobasidium Pullulans ◽  
Culture Medium ◽  
Indoor Dust ◽  
Human Pathogen ◽  
Response Curves ◽  
Colony Diameter ◽  
First Time ◽  
Lower Tolerance

We isolated the human pathogen <em>Wallemia mellicola</em> from the class Wallemiomycetes for the first time in Poland. The fungus was isolated from indoor dust in Cracow. The strain belonged to the genus <em>Wallemia</em>, as confirmed by molecular methods (i.e., ITS1-5.8S-ITS2 nrDNA sequencing). We compared the halotolerance and chaotolerance of <em>W. mellicola</em> to other those of halotolerant fungi (<em>Talaromyces diversus</em> and <em>Aureobasidium pullulans</em>) isolated from an anchialine cave. The <em>W. mellicola</em> strain tolerated up to 20% NaCl and up to 15% MgCl<sub>2</sub>. As the concentration of NaCl in the culture medium increased, the colony diameter of <em>W. mellicola</em> decreased slightly. Dose–response curves for the two reference fungi <em>T. diversus</em> and <em>A. pullulans</em> revealed much lower tolerance of these fungi to increasing concentrations of NaCl. Our results indicated that <em>W. mellicola</em> is an advanced kosmotrope that is distinctly adapted to saline environments.

Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas
Keyword(s):  
Dose Response ◽  
Fibrinolytic Activity ◽  
Enzyme Concentration ◽  
Response Curves ◽  
Agar Gel ◽  
Porcine Tissue ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Different Types ◽  
Dose Response Curves

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.

Factor VII Clotting Assay: Influence of Different Thromboplastins and Factor VII-Deficient Plasmas

1991 ◽  
Vol 65 (02) ◽  
pp. 160-164 ◽  
Author(s):  
Marina Poggio ◽  
Armando Tripodi ◽  
Guglielmo Mariani ◽  
Pier Mannuccio Mannucci ◽  
Keyword(s):  
Heart Disease ◽  
Ischemic Heart Disease ◽  
Dose Response ◽  
Response Curve ◽  
Ischemic Heart ◽  
Factor Vii ◽  
Response Curves ◽  
Assay Sensitivity ◽  
Clinical Laboratories ◽  
Coagulant Activity

SummaryBeing a putative predictor of ischemic heart disease, the measurement of factor VII (FVTI) coagulant activity will be presumably requested to clinical laboratories with increasing frequency. To assess the influence on FVII assays of different thromboplastins and FVII-deficient plasmas we compared performances of all possible combinations of 5 thromboplastins and 6 deficient plasmas. The reproducibility of the clotting times of the dose-response curves for human and rabbit thromboplastins were acceptable (CV lower than 7%), whereas bovine thromboplastin had a higher CV. Reproducibility was very similar for all deficient plasmas when they were used in combination with a given thromboplastin. Responsiveness of the dose-response curve did not depend on the deficient plasma but rather on the thromboplastin: one rabbit thromboplastin was the least responsive, the bovine thromboplastin the most responsive, the human and the remaining two rabbit thromboplastins had intermediate responsiveness. Assay sensitivity to cold-activated FVII varied according to the thromboplastin: the bovine thromboplastin was the most sensitive, the human thromboplastin the least sensitive, of the three rabbit thromboplastins two were relatively sensitive, one was almost insensitive. In conclusion, our results indicate that thromboplastin rather than deficient plasma is the crucial factor in the standardization of FVII assay.

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

BIOASSAY OF THYROID HORMONE USING HYPOTHYROID TADPOLES

1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques
Keyword(s):  
Thyroid Hormone ◽  
Dose Response ◽  
Developmental Rate ◽  
Response Curves ◽  
Sodium Salts ◽  
Dose Response Curves

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.

ÜBER DIE ANTAGONISTISCHE WIRKUNG VON TRIJODTHYRONIN UND PROGESTERON AUF DEN PREDNISOLONEFFEKT AM EPIPHYSENKNORPEL (PRÜFUNG DER REISSFESTIGKEIT)

1963 ◽  
Vol 42 (1) ◽  
pp. 29-38 ◽  
Author(s):  
L. Ther ◽  
H. Schramm ◽  
G. Vogel
Keyword(s):  
Tensile Strength ◽  
Dose Response ◽  
Single Injection ◽  
Relative Effectiveness ◽  
Prednisolone Acetate ◽  
Response Curves ◽  
Deoxycorticosterone Acetate ◽  
Weight Range ◽  
Diuretic Action ◽  
Maximal Load

ABSTRACT Longitudinal tension exerted on a killed rat's femur results always in rupture on the same place viz: the distal epiphyseal line. The power required to produce this effect can be measured with a simple dynamometer. The tensile strength increases with advancing age and during exsiccation (thirst). In untreated rats (weight range 100–120 g) this value amounts to about 1.5–1.8 kg. Tensile strength of the femoral epiphyseal line may be influenced by hormones. Corticosteroids such as prednisolone acetate and cortisol acetate increase the level of maximal load to more than 2.0 kg. In general the effect of a single injection reaches a climax after 48 hours. Dose-response-curves can be established and relative effectiveness may be gathered therefrom. Deoxycorticosterone acetate likewise increases tensile strength in spite of the fact that contrary to prednisolone exhibiting diuretic action this compound has a water retaining effect. Triiodothyronine and progesterone when given alone produce a slight decrease in tensile strength. The effect of prednisolone when given simultaneously with one of these two compounds is antagonized: this phenomenon is more pronounced in the case of triiodothyronine.

Dose Response Curves for Microwave Ablation in the Cardioplegia-Arrested Porcine Heart

2005 ◽  
Vol 8 (4) ◽  
pp. E269-E274 ◽  
Author(s):  
Sydney L. Gaynor ◽  
Gregory D. Byrd ◽  
Michael D. Diodato ◽  
Yosuke Ishii ◽  
Anson M. Lee ◽  
...  
Keyword(s):  
Dose Response ◽  
Microwave Ablation ◽  
Response Curves ◽  
Porcine Heart ◽  
Dose Response Curves

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C–H Activation

2020 ◽  
Author(s):  
Chang-Sheng Wang ◽  
Sabrina Monaco ◽  
Anh Ngoc Thai ◽  
Md. Shafiqur Rahman ◽  
Chen Wang ◽  
...  
Keyword(s):  
Catalytic System ◽  
Lewis Acid ◽  
Hydrogen Transfer ◽  
Acid Catalysis ◽  
Rate Limiting Step ◽  
Site Selectivity ◽  
Set Up ◽  
Site Selective ◽  
First Time ◽  
Rate Limiting

A catalytic system comprised of a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic system for analogous transformations, the present catalytic system not only feature convenient set up using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp), but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Mechanistic stidies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkyl(carbamoyl)cobalt intermediate.

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