Endoplasmic reticulum stress induces autophagy through activation of p38 MAPK in fibroblasts from Pompe disease patients carrying c.546G&gt;T mutation

Shimada, Yohta; Kobayashi, Hiroshi; Kawagoe, Shiho; Aoki, Katsuhiko; Kaneshiro, Eiko; Shimizu, Hiromi; Eto, Yoshikatsu; Ida, Hiroyuki; Ohashi, Toya

doi:10.1016/j.ymgme.2011.09.005

Cited by 41 publications

(43 citation statements)

References 39 publications

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“…During autophagy, cellular components are engulfed by the double-membrane autophagosome, which fuses with lysosomes to degrade the internal contents. We and others have previously reported that autophagosomes accumulate in fibroblasts from patients with Pompe disease [8,9]. We also demonstrated that mutant GAA-induced endoplasmic reticulum (ER) stress is involved in the induction of autophagy in fibroblasts from patients [8].…”

Section: Introductionsupporting

confidence: 53%

Akt inactivation induces endoplasmic reticulum stress-independent autophagy in fibroblasts from patients with Pompe disease

Nishiyama

Shimada

Yokoi

et al. 2012

Molecular Genetics and Metabolism

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Section: Introductionsupporting

confidence: 53%

Akt inactivation induces endoplasmic reticulum stress-independent autophagy in fibroblasts from patients with Pompe disease

Nishiyama

Shimada

Yokoi

et al. 2012

Molecular Genetics and Metabolism

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“…ER stress has been shown to trigger autophagy in the kidney and other tissues. [26][27][28] In fact the observed activation of the ER stress-induced apoptotic pathway in 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594the kidneys of our untreated Imai rats was accompanied by marked upregulation of LC3, which is a well-known marker of autophagy.…”

Section: Resultsmentioning

confidence: 99%

Participation of endoplasmic reticulum stress in the pathogenesis of spontaneous glomerulosclerosis–Role of intra-renal angiotensin system

Aminzadeh

Satô

Vaziri

2012

Translational Research

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“…The pH-sensitive dye BCECF was used for the recording of intracellular pH, using a spectrofluorometric method that measures the fluorescence intensity ratio of intracellular dye (24,42). In brief, after differentiation for 48 h in six-well plates, cells were loaded with BCECF-AM (1 M in DMSO).…”

Section: Methodsmentioning

confidence: 99%

Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis

Qiu¹,

Tsien

Thapalaya³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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SV, Dasarathy S. Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab 303: E983-E993, 2012. First published August 14, 2012; doi:10.1152/ajpendo.00183.2012.-Hyperammonemia and sarcopenia (loss of skeletal muscle) are consistent abnormalities in cirrhosis and portosystemic shunting. We have shown that muscle ubiquitin-proteasome components are not increased with hyperammonemia despite sarcopenia. This suggests that an alternative mechanism of proteolysis contributes to sarcopenia in cirrhosis. We hypothesized that autophagy could be this alternative pathway since we observed increases in classic autophagy markers, increased LC3 lipidation, beclin-1 expression, and p62 degradation in immunoblots of skeletal muscle protein in cirrhotic patients. We observed similar changes in these autophagy markers in the portacaval anastamosis (PCA) rat model. To determine the mechanistic relationship between hyperammonemia and autophagy, we exposed murine C2C12 myotubes to ammonium acetate. Significant increases in LC3 lipidation, beclin-1 expression, and p62 degradation occurred by 1 h, whereas autophagy gene expression (LC3, Atg5, Atg7, beclin-1) increased at 24 h. C2C12 cells stably expressing GFP-LC3 or GFPmCherry-LC3 constructs showed increased formation of mature autophagosomes supported by electron microscopic studies. Hyperammonemia also increased autophagic flux in mice, as quantified by an in vivo autophagometer. Because hyperammonemia induces nitration of proteins in astrocytes, we quantified global muscle protein nitration in cirrhotic patients, in the PCA rat, and in C2C12 cells treated with ammonium acetate. Increased protein nitration was observed in all of these systems. Furthermore, colocalization of nitrated proteins with GFP-LC3-positive puncta in hyperammonemic C2C12 cells suggested that autophagy is involved in degradation of nitrated proteins. These observations show that increased skeletal muscle autophagy in cirrhosis is mediated by hyperammonemia and may contribute to sarcopenia of cirrhosis.

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Endoplasmic reticulum stress induces autophagy through activation of p38 MAPK in fibroblasts from Pompe disease patients carrying c.546G>T mutation

Cited by 41 publications

References 39 publications

Akt inactivation induces endoplasmic reticulum stress-independent autophagy in fibroblasts from patients with Pompe disease

Akt inactivation induces endoplasmic reticulum stress-independent autophagy in fibroblasts from patients with Pompe disease

Participation of endoplasmic reticulum stress in the pathogenesis of spontaneous glomerulosclerosis–Role of intra-renal angiotensin system

Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis

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