Degradation of endocytosed proteins is unaltered in senescent human fibroblasts

Gurley, Rebecca C.; Jf, Dice

doi:10.1016/0309-1651(88)90052-5

Cited by 16 publications

(4 citation statements)

References 19 publications

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“…The degradation of this desialyated glycoprotein was similar in hepatocytes isolated from the three groups of mice. This observation is consistent with the report by Gurley and Dice (113) showing that the rate of degradation of endocytosed proteins was similar in early-and latepassage human fibroblasts.…”

Section: Effect Of Age On the Degradation Of Specific Proteinssupporting

confidence: 93%

Effect of age on liver protein synthesis and degradation

Ward

Richardson

1991

Hepatology

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Section: Effect Of Age On the Degradation Of Specific Proteinssupporting

confidence: 93%

Effect of age on liver protein synthesis and degradation

Ward

Richardson

1991

Hepatology

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“…Nevertheless, neither the maturation nor the degradation capabilities of vesicles were affected. Our findings support the conclusion of Gurley and Dice that there are no differences in the intralysosomal degradation rates of several endocytosed proteins between young and senescent fibroblast cells (Gurley and Dice, 1988). On the other hand, there are reports that senescent cells undergo receptor-mediated endocytosis changes (Park et al, 2001b;Park et al, 2002).…”

Section: Discussionsupporting

confidence: 92%

Staphylococcus aureus phagocytosis is affected by senescence

Robledo,

Benito Rodriguez,

Vega

et al. 2023

Front. Aging

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Senescent cells accumulate in multicellular animals with aging, resulting in organ or tissue dysfunction. These alterations increase the incidence of a variety of illnesses, including infectious diseases, and, in certain instances, its severity. In search of a rationale for this phenomenon, we focused on the endophagocytic pathway in senescent cells. We first described the endocytic vesicle populations at different stages of maturation using confocal microscopy. There was an increase in the number of vacuoles per cell, which was partially explained by an increase in cell size. No changes in vesicle maturation or degradation capacities were determined by microscopy or Western blot assays. Also, we studied the internalization of various endophagocytic cargoes in senescent cells and observed only a decrease in the intracellular recovery of bacteria such as Staphylococcus aureus. Afterwards, we studied the intracellular traffic of S. aureus, and observed no differences in the infection between control and senescent cells. In addition we quantified the recovery of bacteria from control and senescent cells infected in the presence of several inhibitors of endophagosomal maturation, and no changes were observed. These results suggest that bacterial internalization is affected in senescent cells. Indeed, we confirmed this hypothesis by determining minor bacterial adherence and internalization by confocal microscopy. Furthermore, it is important to highlight that we found very similar results with cells from aged animals, specifically BMDMs. This alteration in senescent cells enlightens the diminished bacterial clearance and may be a factor that increases the propensity to suffer severe infectious conditions in the elderly.

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“…To determine how much mAb 13D3 would be needed to neutralize ly-hsc73, we radiolabeled mAb 13D3 with NaB 3 H 4 and determined the amount of [ 3 H]mAb 13D3 that could be endocytosed by fibroblasts and its half-life after endocytosis. These studies indicated that mAb 13D3 was internalized by absorptive endocytosis at 12 times the rate of [ 3 H]sucrose, a fluid-phase marker (Gurley and Dice, 1988), and it had a half-life within lysosomes of 45 h (data not shown). The previous quantitation of the amount of ly-hsc73 (Terlecky and Dice, 1993) allowed us to calculate that overnight endocytosis of 10 g/ml of mAb 13D3 should result in an eightfold molar excess of mAb 13D3 over ly-hsc73.…”

Section: Role Of Ly-hsc73 In the Hsc73-stimulated Lysosomal Proteolytic Pathwaymentioning

confidence: 97%

An Intralysosomal hsp70 Is Required for a Selective Pathway of Lysosomal Protein Degradation

Agarraberes

Terlecky

Dice

1997

The Journal of Cell Biology

290

270

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Previous studies have implicated the heat shock cognate (hsc) protein of 73 kD (hsc73) in stimulating a lysosomal pathway of proteolysis that is selective for particular cytosolic proteins. This pathway is activated by serum deprivation in confluent cultured human fibroblasts. We now show, using indirect immunofluorescence and laser scanning confocal microscopy, that a heat shock protein (hsp) of the 70-kD family (hsp70) is associated with lysosomes (ly-hsc73). An mAb designated 13D3 specifically recognizes hsc73, and this antibody colocalizes with an antibody to lgp120, a lysosomal marker protein. Most, but not all, lysosomes contain ly-hsc73, and the morphological appearance of these organelles dramatically changes in response to serum withdrawal; the punctate lysosomes fuse to form tubules.Based on susceptibility to digestion by trypsin and by immunoblot analysis after two-dimensional electrophoresis of isolated lysosomes and isolated lysosomal membranes, most ly-hsc73 is within the lysosomal lumen. We determined the functional importance of the ly-hsc73 by radiolabeling cellular proteins with [3H]leucine and then allowing cells to endocytose excess mAb 13D3 before measuring protein degradation in the presence and absence of serum. The increased protein degradation in response to serum deprivation was completely inhibited by endocytosed mAb 13D3, while protein degradation in cells maintained in the presence of serum was unaffected. The intralysosomal digestion of endocytosed [3H]RNase A was not affected by the endocytosed mAb 13D3. These results suggest that ly-hsc73 is required for a step in the degradative pathway before protein digestion within lysosomes, most likely for the import of substrate proteins.

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Degradation of endocytosed proteins is unaltered in senescent human fibroblasts

Cited by 16 publications

References 19 publications

Effect of age on liver protein synthesis and degradation

Effect of age on liver protein synthesis and degradation

Staphylococcus aureus phagocytosis is affected by senescence

An Intralysosomal hsp70 Is Required for a Selective Pathway of Lysosomal Protein Degradation

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