Cathepsin-regulated apoptosis

Abstract

Apoptosis can be mediated by different mechanisms. There is growing evidence that different proteolytic enzymes are involved in the regulation of apoptosis. Cathepsins are proteases which, under physiologic conditions, are localized intralysosomally. In response to certain signals they are released from the lysosomes into the cytoplasm where they trigger apoptotic cell death via various pathways, including the activation of caspases or the release of proapoptotic factors from the mitochondria. Here, we review different mechanisms that induce the release of lysosomal enzymes, and the functional relevance of defined cathepsins in defined models of apoptosis.

Identification of genes involved in gentamicin-induced nephrotoxicity in rats – A toxicogenomic investigation

“…As possible mechanisms, destabilization of the lysosomal membrane with the subsequent release of cathepsins but also effects of cytosolic gentamicin on mitochondria or the impairment of Bax (BCL2-associated X protein) protosomal degradation were suggested (Chwieralski et al 2006;Servais et al, 2008). In our study we found an up-regulation of CTSL2 (Cathepsin L2) which might reflect the activation of apoptosis.…”

Identification and characterization of hypoxia-induced genes in Carassius auratus blastulae embryonic cells using suppression subtractive hybridization

“…Both low and high oxygen levels have been reported to cause apoptosis by releasing of cytochrome c from mitochondria (Malhotra et al, 2001;Greijer and van der Wall, 2004;Zhang et al, 2005). In apoptosis, caspases, a family of cysteine proteases, have been identified to initiate the apoptotic pathway (Fan et al, 2005;Chwieralski et al, 2006;Conus et al, 2008). In our study, the expression of several cathepsin genes (cathepsin D, Z, L) and tumor protein p53 increased following 24-h hypoxia treatment.…”

Macrophage and microglia ontogeny in the mouse visual system can be traced by the expression of Cathepsins B and D

“…Cathepsins have been described as being involved in programmed cell death that occurs under experimental and disease conditions in various forms, such as apoptosis, autophagy, among others Lockshin and Zakeri, 2002;Guicciardi et al, 2004;Chwieralski et al, 2006;Boya and Kroemer, 2008;Johansson et al, 2010). However, to date the role of cathepsins in retinal cell death has received little attention.…”

“…While it is firmly established that cathepsins play a role in programmed cell death in different tissues by their translocation from the lysosomal lumen into the cytosol in response to a variety of signals (Yamashima, 2000;Foghsgaard et al, 2001;Kagedal et al, 2001;Leist and Jaattela, 2001;Locksin and Zakeri, 2002;Jaattela et al, 2004;Chwieralski et al, 2006;Zuzarte-Luis et al, 2007a,b), the evidence for a pivotal role of individual cathepsins in ontogenetic cell death is either weak or negative. Recently it has been shown that the expression of cathepsin B and D genes coincides with the spatial distribution of areas of apoptosis during avian embryonic development (Zuzarte-Luis et al, 2007a,b).…”