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. Author manuscript; available in PMC: 2014 Jul 9.
Published in final edited form as: Photochem Photobiol Sci. 2011 Jul 20;11(1):163–172. doi: 10.1039/c1pp05131h

Fig. 4. Cathepsin B inactivation as a causative factor in cutaneous UVA photodamage operating upstream of autophagic-lysosomal alterations.

Fig. 4

The model proposes that inactivation of cathepsin B as a consequence of either UVA-induced photooxidative stress (mediated by ROS) or direct pharmacological antagonism (by the specific inhibitor CA074Me) causes authophagic-lysosomal dysregulation. Effects of chronic UVA exposure on phenotypic markers including cellular autofluorescence (not shown) and lysotracker Red staining (confocal microscopy images, panels as in Fig. 1G) the expression pattern of the autophagic-lysosomal factors Lamp-1, LC3-II, beclin 1, p62, α-synuclein, and transglutaminase 2 are mimicked by CA074Me treatment indicating that UVA exposure causes autophagic-lysosomal dysregulation downstream of cathepsin B inactivation, a novel molecular mechanism potentially involved in UVA-induced skin photodamage. Differential stress response gene expression (including heat shock protein encoding genes) occurs in response to UVA but not CA074Me due to the causative involvement of ROS in UVA-induced cathepsin B inhibition that are not generated as a result of direct pharmacological antagonism by CA074Me.