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Updated: May 9, 2026
Optimized Automated Analysis of Live Neuronal Mitochondria Homeostasis Modulation by Isoform-Specific Retinoic Acid Receptors
Published on: July 28, 2023
Biphasic pro-melanogenic and pro-apoptotic effects of all-trans-retinoic acid (ATRA) on human melanocytes:
Ioana Baldea1, Gertrude-Emilia Costin, Yiqun Shellman
1Department of Physiology, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania.
Background:
The effects of retinoids on melanogenesis and their mechanism as depigmenting agents in topical therapy have not been fully elucidated. Conflicting data about their impact on melanogenic pathways have been reported.
Objective:
To investigate the effects of all-trans-retinoic acid (ATRA) on normal human melanocytes from Caucasian subjects.
Methods:
We assessed ATRA's cytotoxicity by measuring viability with a cell proliferation assay, and apoptotic effects using Annexin V and γ-H2AX markers. ATRA's melanogenic activity was investigated based on spectrophotometric measurement of melanin content and tyrosinase enzymatic activity. Tyrosinase expression was assessed by Western blotting. We tested the antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) in melanocytes using a spectrophotometric assay.
Results:
Of the concentrations tested in this 72h time-course study, the 1.0μM ATRA had a well-defined two-stage pro-melanogenic and pro-apoptotic effect on melanocytes. In the first 6h, treated cells showed significant increase (p≤0.01) of melanin content, tyrosinase, SOD, and CAT activities compared to the controls. While overall tyrosinase expression was not affected by ATRA, all other tested parameters decreased progressively beyond the short-term point of 6h. ATRA treatment of over 6h induced melanocyte apoptosis, as shown by the time-dependent decrease in cell viability, coupled with significant increase in Annexin V positive cells and nuclear accumulation of γ-H2AX foci.
Conclusion:
The results obtained using this testing platform show a biphasic ATRA action: immediate pro-melanogenic effect and longer-term exposure pro-apoptotic activity. These data qualify ATRA as a potent tool to better understand the mechanisms that regulate the pigmentary system.
Insights
All-trans-retinoic acid (ATRA) has a biphasic effect on melanocytes, initially promoting melanin production and antioxidant activity, then inducing apoptosis with longer exposure. This reveals ATRA
Area of Science:
- Dermatology
- Cell Biology
- Biochemistry
Background:
- The precise effects of retinoids on melanogenesis remain unclear, with existing research presenting conflicting data on their impact on melanogenic pathways.
- Understanding retinoids' mechanisms as depigmenting agents in topical therapies is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effects of all-trans-retinoic acid (ATRA) on normal human melanocytes derived from Caucasian individuals.
- To elucidate the biphasic action of ATRA on melanogenesis and melanocyte apoptosis.
Main Methods:
- Cytotoxicity and apoptosis were assessed using cell proliferation assays, Annexin V, and γ-H2AX markers.
- Melanogenic activity was evaluated by measuring melanin content and tyrosinase activity.
- Tyrosinase expression, and antioxidant enzyme activities (SOD, CAT) were analyzed.
Main Results:
- A 1.0μM concentration of ATRA demonstrated a biphasic effect over 72 hours.
- Short-term exposure (≤6h) increased melanin content, tyrosinase, SOD, and CAT activities.
- Longer exposure (>6h) led to decreased cell viability, increased Annexin V positive cells, and γ-H2AX foci, indicating apoptosis.
Conclusions:
- ATRA exhibits an immediate pro-melanogenic effect followed by a longer-term pro-apoptotic activity in human melanocytes.
- These findings highlight ATRA's potential as a tool for studying pigmentary system regulation.
