Biology Reference
In-Depth Information
Table 2.1 Extracellular matrix proteins degraded by cathepsins
ECM protein
Cathepsin
Proteoglycan:
Cathepsin B, L (Maciewicz and Wotton
1991
; Roughley and
Barrett
1977
)
Aggrecan
Cathepsin K, L, S (Hou et al.
2003
; Nguyen et al.
1990
)
Cathepsin B (Fosang et al.
1992
; Mort et al.
1998
; Nguyen et al.
1990
)
Fibers: Collagen
Cathepsin S (Maciewicz and Etherington
1988
; Xin et al.
1992
)
Fibrillar (type I, II, III, V, XI)
Cathepsin B, L: coll II, IX, XI (Maciewicz et al.
1990
)
Facit (type IX, XII, XIV)
Cathepsin B: coll IV, X coll (Buck et al.
1992
; Sires et al.
1995
)
Short chain (type VIII, X)
Cathepsin K: coll I, II (Bromme et al.
1996
; Garnero et al.
1998
;
Kafienah et al.
1998
; Nosaka et al.
1999
)
Basement membrane (type IV)
Cathepsin L: coll I (Nosaka et al.
1999
)
Other (type VI, VII, XIII)
Elastin
Cathepsin S (Shi et al.
1992
; Xin et al.
1992
)
Cathepsin L (Kitamoto et al.
2007
; Mason et al.
1986
)
Cathepsin V (Yasuda et al.
2004
)
Cathepsin K (Br
omme et al.
1996
)
€
Fibronectin
Cathepsin B (Buck et al.
1992
; Isemura et al.
1981
)
Cathepsin L (Ishidoh and Kominami
1995
)
Cathepsin S (Taleb et al.
2006
)
Laminin
Cathepsin B (Buck et al.
1992
)
Cathepsin L (Ishidoh and Kominami
1995
)
Osteocalcin
Cathepsin B; Arg44-Phe45 (Baumgrass et al.
1997
)
Cathepsin S, H, B; Gly7-Ala8 (Baumgrass et al.
1997
)
Cathepsin L; Gly7-Ala8, Arg43-Arg44 (Baumgrass
et al.
1997
)
Cathepsin D; Ala41-Tyr42 (Baumgrass et al.
1997
)
Osteonectin
Cathepsin K (Bossard et al.
1996
)
Cathepsin B (Page et al.
1993
)
(Riese et al.
1998
). Cathepsin S also exhibits a potent elastolytic activity (Bromme
et al.
1993
; Shi et al.
1992
). Its high expression levels in macrophages and the
accumulation of these cells at sites of inflammation and tissue destruction made
cathepsin S an early candidate for ECM degradation (Shi et al.
1992
). Furthermore,
cathepsin S expression is also induced in kerotincytes and smooth muscle cells in the
presence of proinflammatory stimuli (Schonefuss et al.
2009
; Watari et al.
2000
)that
seem to trigger the secretion of cathepsin S (Lackman et al.
2007
).
A second explanation for how cathepsins can degrade ECM is that the activity of
secreted cathepsins in the ECM is facilitated by the acidification of the peri- and
extracellular space under inflammatory conditions. pH values as low as 5 have been
reported at sites of cartilage erosion in arthritic joints and in atherosclerotic plaques
(Konttinen et al.
2002
; Naghavi et al.
2002
). Pericellular pH values in inflamed
tissues or tumors can be significantly below the physiological pH of 7.4 and thus
allowing pH labile cathepsins to be active. In particular, macrophages tolerate pH
changes in the pericellular environment (Silver
1975
; Silver et al.
1988
). Moreover,
pericellular acidic pH values seem to increase the redistribution of lysosomes to the
cell surface and the subsequent secretion of lysosomal proteases as it has been
demonstrated for cathepsin B (Rozhin et al.
1994
). Extracellular acidification is not
