The sarcoplasmic reticulum plays a pivotal role in regulating muscle contraction given its role in in storage, release and reuptake of Ca2+. Release of calcium from the sarcoplasmic reticulum occurs through the so-called excitation-contraction coupling mechanism that consists in the activation of voltage-induced calcium channels on the plasma membrane (DHPR) with the consequent opening of ryanodine receptors type 1 (RyR1) on the sarcoplasmic reticulum. Mutations in the gene coding for RyR1 were identified in a significant fraction of human congenital myopathies, defined as RyR1-related myopathies (RyR-RM). Among these, Central Core Disease (CCD) represents the most common inherited congenital myopathy and is characterized by the presence of cores, i.e. areas lacking oxidative enzymes due to depletion of mitochondria, accompanied also by alterations in calcium homeostasis, ultrastructural modifications and induction of cellular dysfunctions such as oxidative/nitrosative stress. Recently, endoplasmic reticulum (ER) stress has been also suggested to play a relevant role in the pathophysiology of muscle disorders. ER stress is activated by a variety of conditions, including alteration in calcium homeostasis, which may lead to the accumulation of misfolded proteins and thus trigger the Unfolded Protein Response (UPR). Deregulation of ER stress/UPR is observed in many muscular diseases, including a mouse model of CCD. In order to evaluate whether ER stress markers are also deregulated in muscles from human patients affected by CCD, expression of selected ER stress-related genes has been analyzed by real-time PCR in muscle biopsies from a cohort of twenty-two unrelated CCD patients and compared with that of healthy controls. No significant changes in expression of ER stress markers were observed in these biopsies indicating that pathogenic mechanism other than ER stress/UPR may be active in humans.

Catallo, m.r. (2022). EVALUATION OF ENDOPLASMIC RETICULUM (ER) STRESS MARKERS IN SKELETAL MUSCLE BIOPSIES FROM PATIENTS AFFECTED BY CENTRAL CORE DISEASE.

EVALUATION OF ENDOPLASMIC RETICULUM (ER) STRESS MARKERS IN SKELETAL MUSCLE BIOPSIES FROM PATIENTS AFFECTED BY CENTRAL CORE DISEASE

catallo, maria rosaria
2022

Abstract

The sarcoplasmic reticulum plays a pivotal role in regulating muscle contraction given its role in in storage, release and reuptake of Ca2+. Release of calcium from the sarcoplasmic reticulum occurs through the so-called excitation-contraction coupling mechanism that consists in the activation of voltage-induced calcium channels on the plasma membrane (DHPR) with the consequent opening of ryanodine receptors type 1 (RyR1) on the sarcoplasmic reticulum. Mutations in the gene coding for RyR1 were identified in a significant fraction of human congenital myopathies, defined as RyR1-related myopathies (RyR-RM). Among these, Central Core Disease (CCD) represents the most common inherited congenital myopathy and is characterized by the presence of cores, i.e. areas lacking oxidative enzymes due to depletion of mitochondria, accompanied also by alterations in calcium homeostasis, ultrastructural modifications and induction of cellular dysfunctions such as oxidative/nitrosative stress. Recently, endoplasmic reticulum (ER) stress has been also suggested to play a relevant role in the pathophysiology of muscle disorders. ER stress is activated by a variety of conditions, including alteration in calcium homeostasis, which may lead to the accumulation of misfolded proteins and thus trigger the Unfolded Protein Response (UPR). Deregulation of ER stress/UPR is observed in many muscular diseases, including a mouse model of CCD. In order to evaluate whether ER stress markers are also deregulated in muscles from human patients affected by CCD, expression of selected ER stress-related genes has been analyzed by real-time PCR in muscle biopsies from a cohort of twenty-two unrelated CCD patients and compared with that of healthy controls. No significant changes in expression of ER stress markers were observed in these biopsies indicating that pathogenic mechanism other than ER stress/UPR may be active in humans.
Catallo, m.r. (2022). EVALUATION OF ENDOPLASMIC RETICULUM (ER) STRESS MARKERS IN SKELETAL MUSCLE BIOPSIES FROM PATIENTS AFFECTED BY CENTRAL CORE DISEASE.
Catallo, maria rosaria
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11365/1211894