Photomodulation of the Melanocyte Cell Cycle by Indoleamines

Abstract

Melanocytes are photoresponsive cells which respond to varying doses of UV exposure in the G₂ phase of the cell cycle by prominent dendricity. This photoresponse is related to indoleamine light sensitivity. The present study highlights the role of indoleamines in the photomodulation of the melanocyte cell cycle. The study was conducted on 40 whole-skin organ cultures taken from the marginal zone of vitiligo. Twenty organ cultures were subjected to G₂-phase arrest, while 20 were incubated in tryptamine. The organ cultures were incubated in the dark, exposed to a pulse of 120 s UV at 2 h of incubation and harvested 3 and 6 h after UV exposure. It has been reported that the photosensitive enzymes N-acetyl transferase (NAT) and hydroxyindole-o-methyl transferase (HIOMT) are activated during the G₂ phase. The conversion of serotonin to melatonin is inhibited by UV exposure as seen at 3 h. This activity recovers on continued dark incubation 6 h after UV exposure. On incubation with tryptamine, UV exposure results in utilisation of tryptamine as seen by prominent indoleamine positivity. Three hours after UV exposure, there is 75% dendricity indicating G₂ phase traverse. There is a corresponding high serotonin positivity with a low melatonin positivity. This is reversed following 6 h of dark incubation with high melatonin positivity indicating reactivation of NAT and HIOMT. This is accompanied by a doubling of the melanocyte number due to mitotic traverse and an arrest in G₁ phase with low utilisation of tryptamine. Thus tryptamine is utilised by melanocytes on UV exposure to be synchronised and traversed into G₂ phase activating the photosensitive enzymes NAT and HIOMT. When followed by a dark phase, melatonin accumulates to traverse the melanocytes through M-phase of the cell cycle with doubling of the cell number. Thus the uptake and metabolisation of indoleamine precursors photomodulate the melanocyte cell cycle on UV exposure.

Melatonin and Melanocyte Functions

“…It was further discovered that melatonin is important for mitotic activity in most lower organisms [2]. From studies in this laboratory, it has been observed that melatonin modulates the melanocyte cell cycle [3], and that indoleamines are expressed by and control melanocytes during the photoresponse [4][5][6]. Several workers have identified indoleamine activity in the skin [7,8].…”

Tumor Vascular Interaction in Melanomas and Neurogenesis: A Review

“…Earlier studies have identified the presence of biogenic amines in melanocytes. These include catechol amines as well as indole amines [2][3][4][5][6][7].…”

“…Since this activity is cyclical with light and dark phases, both SER & MLT are expressed in these layers. In turn, the indoleamines modulate the melanocyte cell cycle in response to UV exposure [4][5][6][7].…”

Biogenic amines and tumor-vascular interaction in melanomas

“…The conversion of serotonin to melatonin is inhibited on exposure to a pulse of UV indicating the presence of the light sensitive enzymes NAT/HIOMT. 5 The epidermal melanocytes metabolise tryptamine 29 to produce indoleamines on UV exposure in whole skin organ cultures. In the TVC, indoleamines are positive in L2/L3 associated with mitosis.…”

“…In turn, the indoleamines modulate the melanocyte cell cycle in response to UV exposure. [4][5][6] Tyrosine is metabolised by several cell types which include catecholaminergic neurones in the brain and spinal cord, 31 sympathetic ganglia, adrenal medulla, and melanocytes which are neuroectodermal in origin. The metabolic pathway is through conversion of tyrosine to dopa, by catecholoxidase, a triphasic enzyme which catalyses both wings of dopa metabolism.…”