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  1. Pubblicazioni

BNIP3 Downregulation Ameliorates Muscle Atrophy in Cancer Cachexia

Articolo
Data di Pubblicazione:
2024
Abstract:
Background and Aims: Cancer cachexia is a complex syndrome affecting most cancer patients and is directly responsible for about 20% of cancer-related deaths. Previous studies showed muscle proteolysis hyper-activation and mitophagy induction in tumor-bearing animals. While basal mitophagy is required for maintaining muscle mass and quality, excessive mitophagy promotes uncontrolled protein degradation, muscle loss and impaired function. BNIP3, a key mitophagy-related protein, is significantly increased in the muscles of both mice and human cancer hosts. This study aimed to define the potential of mitigating mitophagy via BNIP3 downregulation in preserving mitochondrial integrity, counteracting skeletal muscle loss in experimental cancer cachexia. Methods: Two in vivo gene delivery methods were performed to knock down muscle BNIP3: electroporation of a BNIP3-specific shRNA expression vector or adenovirus injection. Results: The electroporation effectively reduced muscle BNIP3 in healthy mice but was ineffective in C26 tumor-bearing mice. In contrast, adenovirus-mediated BNIP3 knockdown successfully decreased BNIP3 levels also in tumor hosts. Although BNIP3 knockdown did not impact overall on body or muscle mass, it improved muscle fiber size in C26-bearing miceh2, suggesting partial prevention of muscle atrophy. Mitochondrial respiratory chain complexes (OxPhos) and TOM20 protein levels were consistently rescued, indicating improvements in mitochondrial mass, while H2O2 levels were unchanged among the groups, suggesting that BNIP3 downregulation does not impair the endogenous control of oxidative balance. Conclusions: These findings suggest that a fine balance between mitochondrial disposal and biogenesis is fundamental for preserving muscle homeostasis and highlight a potential role for BNIP3 modulation against cancer-induced muscle wasting.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
BNIP3; cancer cachexia; mitochondria; mitophagy; muscle wasting
Elenco autori:
Fornelli C.; Beltra M.; Zorzano A.; Costelli P.; Sebastian D.; Penna F.
Autori di Ateneo:
COSTELLI Paola
FORNELLI Claudia
PENNA Fabio
Link alla scheda completa:
https://iris.unito.it/handle/2318/2053113
Link al Full Text:
https://iris.unito.it/retrieve/handle/2318/2053113/1523835/82%20Cancers%20BNIP3.pdf
Pubblicato in:
CANCERS
Journal
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Settori (11)


LS4_1 - Organ and tissue physiology and pathophysiology - (2024)

LS4_12 - Cancer - (2024)

LS4_9 - Metabolism and metabolic disorders, including diabetes and obesity - (2024)

CIBO, AGRICOLTURA e ALLEVAMENTI - Farmacologia Veterinaria

CIBO, AGRICOLTURA e ALLEVAMENTI - Patologia e malattie degli animali

CIBO, AGRICOLTURA e ALLEVAMENTI - Scienze cliniche veterinarie

MEDICINA, SALUTE e BENESSERE - Epidemiologia

MEDICINA, SALUTE e BENESSERE - Oncologia e Tumori

MEDICINA, SALUTE e BENESSERE - Ricerca Traslazionale e Clinica

MEDICINA, SALUTE e BENESSERE - Trapianti e medicina rigenerativa

SCIENZE DELLA VITA e FARMACOLOGIA - Interazioni tra molecole, cellule, organismi e ambiente
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