Differential activity of cathepsin L in human placenta at two different stages of gestation.
The implantation of blastocyst depends on the invasiveness of the syncytiotrophoblast, which penetrates the maternal decidua to establish the placenta. Cathepsin L, a lysosomal cysteine protease over-expressed in a variety of human malignancies, has been implicated in tumour invasion and metastasis. Specific inhibitors of cathepsin L inhibit the invasion of amnion by murine tumour cells. Previous studies have revealed that tumour and trophoblast invasiveness are mediated by shared factors, like metalloproteinases and laminin. Several proteases closely related to cathepsin L have recently been reported in the placentae of different species. In the present study, we demonstrate the expression of cathepsin L in human placenta by immunohistochemical analysis and RT-PCR followed by Southern hybridization. The activity of cathepsin L against the synthetic dipeptidyl substrate, Cbz-Phe-Arg-N-Methylcoumarin, was assayed. E-64, a specific inhibitor of cathepsin L was used to confirm that the enzyme activity being measured was due to cathepsin L. We observed the specific activity of cathepsin L in first trimester placenta to be significantly higher as compared to the term placenta. However, the levels of placental cathepsin L mRNA were comparable at these two stages of gestation. The increased enzymatic activity of cathepsin L in the invasive phase of placentation taken together with its previously established role in tumour invasion and metastasis indicates the involvement of this protease in trophoblast invasion.
Divya
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Chhikara
P
P
Mahajan
V S
VS
Datta Gupta
S
S
Chauhan
S S
SS
D000328:Adult; D015139:Blotting, Southern; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007930:Leucine / Q000031:analogs & derivatives / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D010455:Peptides; D012333:RNA, Messenger; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; D007930:Leucine; C024974:E 64