Differential Expression of System L Amino Acid Transporters during Wound Healing Process in the Skin of Young and Old Rats

Abstract

Wound healing process could be considered to be a continuous morphological change of cells including the change of cell migration, adherence, etc.1) Such changes of cells play decisive roles in other biological processes, for example, embryo development, tissue changes or tumor development. 1)Wound healing is a highly developed biological defense mechanism for the prevention of body fluid leakage, protection of the regenerating cellular barrier, and the removal of tissue residues and foreign materials, and it could be considered as a short term process inducing tissue regeneration and the removal of tissue debris for wound healing.2-4) Also, the continuous growth and proliferation of cells are essential for the wound healing, and high protein synthesis may be essential for this.Amino acids are indispensable for protein synthesis and consequently essential for cell growth and proliferation in both normal and transformed cells. 5,6) Amino acid transport across the plasma membrane is mediated via amino acid transporters located on it.5,6) The continuous growth and proliferation of cells requires continuous protein synthesis. It is known that the supply of amino acids for continuous protein synthesis in these cells is mediated by the overexpression of amino acid transporters. [7][8][9] Recently, the system L-type amino acid transporters 1 and 2 (LAT1 and LAT2) were isolated. 7,8,10) They were predicted to be 12-membrane-spanning proteins that mediate Na ϩ -independent amino acid exchange. 7,8,10) They require an additional single-membrane-spanning protein, a heavy chain of 4F2 antigen (4F2hc), for their functional expression in the plasma membrane.7,8,10-14) LAT1 mRNA is only expressed in restricted organs such as the brain, spleen, placenta and testis. 7,8,14,15) However, the mRNAs of LAT2 and 4F2hc are ubiquitously expressed in all normal embryonic and normal adult tissues. 7,8,10,14) In addition, LAT1 is highly expressed in malignant tumors presumably to support their continuous growth and proliferation.7-9,16) The LAT1 prefers large neutral amino acids for its substrates, 7,8,17) while the LAT2 transports not only large neutral amino acids, but also small neutral amino acids, in a fashion that appears to have broader substrate selectivity than LAT1. 10,[18][19][20] It is reported that the system L-type amino acid transporters may be important in living organism, because it is a major route for providing living cells with neutral amino acids including several essential amino acids, which cells are unable to synthesize. 5,6) Thus, the system L may have an essential role in the wound healing process also. However, the expression and functional characterization of amino acid transporters, including the system L, in supplying nutrition to cells in the wound healing process are not known at all.It is suggested that the age-related differences may be present in wound healing process. 21) Although the elderly can heal most wounds, they have a slower healing process, and impaired wound healing in the elderly presents a m...