Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine

Wong, Way W.; Altemus, Jessica; Hester, James; Chan, E. Ricky; Côté, Jean‐François; Serre, David; Sehayek, Ephraim

doi:10.1194/jlr.m034579

Cited by 7 publications

(3 citation statements)

References 14 publications

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“…P11 is associated with cholesterol-rich platforms on endosomal membranes (Morel and Gruenberg, 2007) and CTSB is also involved in peripheral cholesterol absorption (Wong et al, 2013). Hippocampal 24-hydoxycholesterol levels, the form of brain specific cholesterol, was diminished in CTSB KO mice compared to WT (t (10) =2.55, p<0.03; Figure 3K).…”

Section: Resultsmentioning

confidence: 99%

Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function

et al. 2016

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SUMMARY Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here we show that a muscle secretory factor, Cathepsin B (CTSB) protein, is important for cognitive benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. In addition, in male wildtype (WT), but not CTSB knockout (KO) mice running enhanced adult hippocampal neurogenesis and spatial memory. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a multifunctional protein, P11, dependent mechanism. Interestingly, in Rhesus monkeys and humans treadmill exercise elevated CTSB in plasma. In humans CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition.

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Section: Resultsmentioning

confidence: 99%

Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function

et al. 2016

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“… 16 In a study of intestine tissue, CTSB was discovered to have an effect on cholesterol absorption from the intestine. 29 All these studies suggest a possible relationship between cholesterol metabolism and CTSB/CTSL. However, more research is needed to clarify the interplay between cholesterol and lysosomal enzymes.…”

Section: Discussionmentioning

confidence: 96%

Elevated CTSL Gene Expression Correlated with Proinflammatory Cytokines in Omental Adipose Tissue of Patients with Obesity

Zhou¹,

Zhu²,

Li³

et al. 2022

DMSO

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Purpose Cathepsin L (CTSL) and B (CTSB) were lysosomal proteases, and their expression and activity contribute to the progression of inflammation in obese rodents. Our aim was to investigate CTSB and CTSL expression in omental adipose tissue (AT) of patients with obesity and to correlate CTSB and CTSL expression with proinflammatory cytokines (CCL-2, IL-6 and IL-1β). Patients and Methods A total of 12 patients without obesity (NOB) and 51 patients with obesity (OB) were involved in this study. Omental AT was collected from all the participants for RNA extraction. Expressions of CTSB, CTSL and proinflammatory cytokines (CCL-2, IL-6 and IL-1β) were qualified with qRT-PCR. BMI (body mass index) and metabolic parameters were measured. Results The mRNA expression levels of both CTSB and CTSL were upregulated in the OB group (t = 2.693, P < 0.05; t = 2.849, P <0.01) and were related to TC levels (Std.β=0.443, P <0.05; Std.β=0.439, P <0.05). However, only the CTSB level was related to BMI (Std.β=0.261, P <0.05). In multiple regression analysis, CTSL was independently associated with CCL-2, IL-6 and IL-1β levels (Std.β=0.352–0.462, P <0.05). Conclusion CTSB and CTSL gene expressions were elevated in the omental AT of OB group. CTSL, but not CTSB, was positively correlated with proinflammatory cytokines independently, suggesting that the dysregulation of CTSL may play a significant role in the inflammatory process.

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“…Neuropathological CTSB KO studies to date have not compared male and female genders (Table 3). It will be important to assess if gender effects may occur in CTSB KO mice since such effects have been shown to occur in models of anxiety (Czibere et al, 2011) and cholesterol (Wong et al, 2013).…”

Section: Gene Knockout Mice For Target Validation and Drug Discoverymentioning

confidence: 99%

Cathepsin B Gene Knockout Improves Behavioral Deficits and Reduces Pathology in Models of Neurologic Disorders

Hook

Reinheckel

et al. 2022

Pharmacol Rev

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Cathepsin B is a novel gender-dependent determinant of cholesterol absorption from the intestine

Abstract: Abbreviations: ACAT2, acyltransferase 2; Ctsb, cathepsin B; FDR, false discovery rate; NPC1L1, Niemann-Pick C1 like 1; SNP, singlenucleotide polymorphism.

Cited by 7 publications

References 14 publications

Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function

Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function

Elevated CTSL Gene Expression Correlated with Proinflammatory Cytokines in Omental Adipose Tissue of Patients with Obesity

Cathepsin B Gene Knockout Improves Behavioral Deficits and Reduces Pathology in Models of Neurologic Disorders

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