Table 1 The roles of CatB in PCD during multiple diseases progression.
From: Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways
Diseases | Subjects | CatB expression folds change | CatB activity | Cell death type | CatB pathological function | Reference |
|---|---|---|---|---|---|---|
Cerebral ischemia | Rat’s model of permanent middle cerebral artery occlusion and in vitro oxygen and glucose deprivation (OGD) model | 3 | up | Astrocytes and embryonic fibroblast cells | CatB-tBid-mitochondrial apoptotic signaling pathway. | [55] |
Cerebral ischemia | Mouse model of permanent middle cerebral artery | 7 | up | Neurons | Subroutines of necrotic and apoptotic cell death are concomitantly activated by cytoplasmic CatB and the dominant cell death phenotype is determined by the relative speed of each process. | |
Cerebral ischemia | 2-vessel occlusion with hypotension global brain ischemia rat model | 25 | – | Pyramidal neurons of the hippocampus and cortex | Extensive CatB release into the cytoplasm results in delayed neuronal death. | [111] |
Focal cerebral ischemia | Permanent occlusion of the middle cerebral artery mice model | up | up | Neurons | CatB activates caspase-11 and/or caspase-1 pathways inducing neuronal apoptosis. | [61] |
Traumatic brain injury (TBI) | Open-skull controlled cortical impact mouse model | 4 | up | Neurons | CatB induces programmed cell necrosis and mitochondria-mediated apoptotic pathways. | |
Lysosomal storage disorders (LSDs) | Acid sphingomyelinase knockout mouse model; Mucopolysaccharidosis type I mouse model | 4–5 | up | Cerebellar neurons | Microglial CatB extracellular release promotes neuronal death. | |
Parkinson’s disease (PD) | MPTP-induced PD model mice; A53T α-Syn treated BV2 cell | 2–4 | – | Microglia、dopamine neuron | α-Syn activates NLRP3 inflammasomes through microglial endocytosis and subsequent lysosomal CatB release then inducing cell death | [57] |
Alzheimer’s disease (AD) | 5xFAD transgenic mouse | – | down | Cerebrocortical primary cell cultures | S-nitrosylating the lysosomal protease CatB inhibits CatB activity and then induces caspase-dependent neuronal apoptosis. | [40] |
Alzheimer’s disease | Aβ-treated BV2 cell; peptide chromogranin A treated primary microglia; human amyloid precursor protein (hAPP) model mouse | 2–4 | up | Microglia; Primary cortical neurons | Aβ/chromogranin-treated microglia causes the release of CatB into the cytoplasm, causing microglia apoptosis, and CatB is released outside the cell, causing neuronal death. | |
Retinitis pigmentosa | rd10 mouse carried a missense mutation in the Pde6b gene | – | Decreased in lysosomes and increased in the cytoplasm | Photoreceptor cells | CatB translocates to the cytosol and then promotes apoptosis. | [64] |
Hypoxia-ischemia (HI) | Permanent middle cerebral artery occlusion (pMCAO) treated rats | Slightly elevated from 1.5 to 6 h after pMCAO and significantly decreased at 1 day | Significantly increased at 6 h after pMCAO and then gradually decreased | Neonatal cortical neurons | Decreased expression and activity of CatB impairs the autophagic-lysosomal pathway, leading to neuronal death. | [66] |
Spinocerebellar ataxia type 6 | Sca6 KI mouse model | KO | – | Purkinje cells (PC) | Lack of CatB expression accelerates mutant Cav2.1 inclusion formation and increases PC loss. | [65] |
HIV-1 infection | Neurons cultured with HIV-infected macrophage-conditioned media | 2 | up | Neuron | CatB–serum amyloid p component (SAPC) interaction triggers neuronal apoptosis. | [69] |
Myocardial infarction | Aortic banding mice | 3 | up | Cardiomyocyte | CatB regulates cardiomyocyte apoptosis via increasing pro-apoptotic proteins Bax and Bid and abating anti-apoptotic protein Bcl-2 expression. | |
Viral myocarditis | Intraperitoneal injection of coxsackievirus B3 into mice to induce viral myocarditis | 2 | up | Cardiomyocyte | CatB activates the NLRP3 inflammasomes promoting cardiomyocyte pyroptosis. | [71] |
Type 1 diabetes | Rat insulinoma cell line INS-1E | 3 | up | Pancreatic β-cell | Lysosomal membrane permeabilization and CatB leakage contribute to the intrinsic pathway of apoptosis. | [116] |
Diabetic cardiomyopathy | Streptozotocin injection induced diabetes mouse model; high glucose treated Neonatal rat cardiomyocytes to establish an in vitro model. | 1.5 | up | Cardiomyocyte | CatB promotes NLRP3-mediated cardiomyocyte pyroptosis. | [72] |
Kawasaki disease | Candida albicans cell wall extracts induced mouse model | up | up | Endothelial cell | CatB activates the NLRP3 inflammasomes mediating endothelial cell pyroptosis. | [102] |
Sjögren syndrome (SS) | Human salivary gland biopsies | 3–4 | – | Salivary glands | The release of CatB into the cytoplasm results in apoptosis via activation of caspase 1 and BID-caspase 3 pathways. | [74] |
Neonatal onset multisystem inflammatory disease (NOMID) | NOMID patient’s whole blood cell | – | – | Monocyte | CatB contributes to the pyronecrosis of CIAS1 mutant monocytes. | |
Liver injury | Liver fibrosis mice induced by bile duct ligation; free fatty acids treated primary mouse hepatocytes; segmental hepatic ischemia mouse model; TNF-α and actinomycin D treated primary mouse hepatocytes | – | up | Hepatocytes | CatB-tBid-mitochondria-caspase apoptotic signaling pathway. | |
Alcohol-associated liver disease (ALD) | Non-alcoholic fatty liver disease patients’ T cell | 12 | up | Duodenal CD8+ T resident memory (TRM) cells | CatB releases into the cytosol driving the TRM apoptosis. | [119] |
Acute pancreatitis | Acinar cells prepared from the pancreas of rats or mice | up | up | Acinar cell | Small amount of CatB in the cytosol activates apoptosis and large amount of CatB shifts the cell death pathway toward necrosis. | |
Acute pancreatitis | Intraperitoneal injection of cerulein in mice to induce acute pancreatitis | 3 | up | Acinar cell | CatB activates the NLRP3 inflammasome and promotes the caspase-1-induced pyroptosis. | [101] |
