Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization

Arnandis, Teresa; Ferrer-Vicens, Iván; Garcı́a-Trevijano, Elena R.; Miralles, Vicente J.; García, Carlos J. Gómez; Torres, Luís; Viña, Juan R.; Zaragozá, Rosa

doi:10.1038/cdd.2012.46

Cited by 61 publications

(68 citation statements)

References 40 publications

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“…14 Although the molecular events that underlie LMP in the mammary gland remain unclear, the activation of Stat3 and calpain appears to have a prominent role. 14,39 Interestingly, Stat3 transcription is also upregulated and its phosphorylation increased in the rd10 retina at P20, 40 the time point at which we observed LMP in the present study. Moreover, this transcription factor is essential to determine photoreceptor cell fate during retinal development 41 and its cleavage has been linked to calpain activation.…”

Section: Discussionsupporting

confidence: 63%

Lysosomal membrane permeabilization and autophagy blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa

et al. 2014

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Retinitis pigmentosa is a group of hereditary retinal dystrophies that normally result in photoreceptor cell death and vision loss both in animal models and in affected patients. The rd10 mouse, which carries a missense mutation in the Pde6b gene, has been used to characterize the underlying pathophysiology and develop therapies for this devastating and incurable disease. Here we show that increased photoreceptor cell death in the rd10 mouse retina is associated with calcium overload and calpain activation, both of which are observed before the appearance of signs of cell degeneration. These changes are accompanied by an increase in the activity of the lysosomal protease cathepsin B in the cytoplasm of photoreceptor cells, and a reduced colocalization of cathepsin B with lysosomal markers, suggesting that lysosomal membrane permeabilization occurs before the peak of cell death. Moreover, expression of the autophagosomal marker LC3-II (lipidated form of LC3) is reduced and autophagy flux is blocked in rd10 retinas before the onset of photoreceptor cell death. Interestingly, we found that cell death is increased by the induction of autophagy with rapamycin and inhibited by calpain and cathepsin inhibitors, both ex vivo and in vivo. Taken together, these data suggest that calpain-mediated lysosomal membrane permeabilization underlies the lysosomal dysfunction and downregulation of autophagy associated with photoreceptor cell death.

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Section: Discussionsupporting

confidence: 63%

Lysosomal membrane permeabilization and autophagy blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa

et al. 2014

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“…Alternatively, Arnandis et al . (2012) [41] has shown that calpains are responsible for mitochondrial and lysosomal membrane permeabilization during lysosomal-mediated mammary epithelial cell death in mice. Also, milk yield is known to decline as function of many factors after peak lactation, including decrease in alveolar secretory epithelial cell number due to programmed cell death [42].…”

Section: Discussionmentioning

confidence: 99%

Detecting Loci under Recent Positive Selection in Dairy and Beef Cattle by Combining Different Genome-Wide Scan Methods

et al. 2013

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As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP) data generated from dairy and beef cattle (taurine and indicine). The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P<3.17×10−7) population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3) in Brown Swiss (P = 3.82×10−12), and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection.

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“…However, calpains are involved not only in necrosis but also in apoptotic cell death, in which they were shown to process BID into proapoptotic t-BID (Gil-Parrado et al 2002). Moreover, calpains were suggested to translocate to the lysosomal membrane of epithelial cells during mammary gland involution to cleave cytosolic parts of membrane proteins, such as LAMP-2, contributing to LMP and thus triggering apoptotic cell death (Arnandis et al 2012). In addition, it was shown that LMP in mammary epithelium is Stat3-dependent and independent of the executioner caspases caspase-3, -6, and -7.…”

Section: Lysosomes In Apoptosismentioning

confidence: 99%

The Endolysosomal System in Cell Death and Survival

Repnik

Česen

Turk

2013

Cold Spring Harbor Perspectives in Biology

118

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The endocytic pathway is a system specialized for the uptake of compounds from the cell microenvironment for their degradation. It contains an arsenal of hydrolases, including proteases, which are normally enclosed in membrane-bound organelles, but if released to the cytosol can initiate apoptosis signaling pathways. Endogenous and exogenous compounds have been identified that can mediate destabilization of lysosomal membranes, and it was shown that lysosomal proteases are not only able to initiate apoptotic signaling but can also amplify the apoptotic pathways initiated in other cellular compartments. The endocytic pathway also receives cargo destined for degradation via the autophagic pathway. By recycling energy and biosynthetic substrates, and by degrading damaged organelles and molecules, the endocytic system assists the autophagic system in resisting apoptotic stimuli. Steps leading to lysosomal membrane permeabilization and subsequent triggering of cell death as well as the therapeutic potential of intervention in lysosomal membrane permeabilization will be discussed.

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Calpains mediate epithelial-cell death during mammary gland involution: mitochondria and lysosomal destabilization

Cited by 61 publications

References 40 publications

Lysosomal membrane permeabilization and autophagy blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa

Lysosomal membrane permeabilization and autophagy blockade contribute to photoreceptor cell death in a mouse model of retinitis pigmentosa

Detecting Loci under Recent Positive Selection in Dairy and Beef Cattle by Combining Different Genome-Wide Scan Methods

The Endolysosomal System in Cell Death and Survival

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