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Expression of endoplasmic reticulum chaperones in cardiac development.

Papp S, Zhang X, Szabo E, Michalak M, Opas M - Open Cardiovasc Med J (2008)

Bottom Line: We found stress related chaperones were more abundant in embryonic compared to adult hearts, indicating endoplasmic reticulum stress during normal cardiac development.In adult hearts, chaperones are less abundant but there are increased levels of ATF6alpha and ER stress-activated caspases.Thus, protein synthesis during embryonic development does not seem to be as intense a stress as is required for apoptosis that is found during postnatal remodelling.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

ABSTRACT
To determine if cardiogenesis causes endoplasmic reticulum stress, we examined chaperone expression. Many cardiac pathologies cause activation of the fetal gene program, and we asked the reverse: could activation of the fetal gene program during development induce endoplasmic reticulum stress/chaperones? We found stress related chaperones were more abundant in embryonic compared to adult hearts, indicating endoplasmic reticulum stress during normal cardiac development. To determine the degree of stress, we investigated endoplasmic reticulum stress pathways during cardiogenesis. We detected higher levels of ATF6alpha, caspase 7 and 12 in adult hearts. Thus, during embryonic development, there is large protein synthetic load but there is no endoplasmic reticulum stress. In adult hearts, chaperones are less abundant but there are increased levels of ATF6alpha and ER stress-activated caspases. Thus, protein synthesis during embryonic development does not seem to be as intense a stress as is required for apoptosis that is found during postnatal remodelling.

No MeSH data available.


Related in: MedlinePlus

Quantification of ER-resident chaperone levels during mouse heart development. .Quantification of Western blots of ER-resident chaperones. The bar graphs denote an average of minimum 4 experiments. The chaperone protein levels are expressed as a ratio of GAPDH as described in Materials and Methods
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Figure 4: Quantification of ER-resident chaperone levels during mouse heart development. .Quantification of Western blots of ER-resident chaperones. The bar graphs denote an average of minimum 4 experiments. The chaperone protein levels are expressed as a ratio of GAPDH as described in Materials and Methods

Mentions: There are several families of ER chaperones, which work in co-ordinated pairs and/or groups. The calreticulin/calnexin cycle of chaperoning has been well established [23-25]. We first investigated the expression pattern of this pair of chaperones during heart development. We have previously shown that calnexin is not induced by ER stress, but that calreticulin is indeed inducible by ER stress [26]. Fig. (1A) shows that calreticulin expression was higher in embryonic heart tissues compared to their adult counterparts. In particular, calreticulin expression diminished dramatically in ventricular tissue postnatally, and remained low into adulthood (Fig. 1, Fig. 4). Earlier studies have demonstrated a role for ER resident chaperones in embryonic development using knockout mice for specific chaperones [10, 27, 28]. Two chaperones, such as calreticulin and Grp94, were found to be critical in embryonic development, as their deficiency induced embryonic death. When calreticulin was ablated, calreticulin-deficient mouse embryos died at gestational day 14.5 as a result of faulty cardiac organogenesis. The cardiac structural defects included very thin ventricular walls with deep intertrabecular recesses [10, 11]. In line with this gene knockout study, our current data showed higher expression of calreticulin in both mouse embryonic atrial and ventricular tissue than in the adult. Calreticulin expression began to subside 17 days postnatally in both atria and ventricles, and in adult ventricles, calreticulin was barely detectable.


Expression of endoplasmic reticulum chaperones in cardiac development.

Papp S, Zhang X, Szabo E, Michalak M, Opas M - Open Cardiovasc Med J (2008)

Quantification of ER-resident chaperone levels during mouse heart development. .Quantification of Western blots of ER-resident chaperones. The bar graphs denote an average of minimum 4 experiments. The chaperone protein levels are expressed as a ratio of GAPDH as described in Materials and Methods
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570582&req=5

Figure 4: Quantification of ER-resident chaperone levels during mouse heart development. .Quantification of Western blots of ER-resident chaperones. The bar graphs denote an average of minimum 4 experiments. The chaperone protein levels are expressed as a ratio of GAPDH as described in Materials and Methods
Mentions: There are several families of ER chaperones, which work in co-ordinated pairs and/or groups. The calreticulin/calnexin cycle of chaperoning has been well established [23-25]. We first investigated the expression pattern of this pair of chaperones during heart development. We have previously shown that calnexin is not induced by ER stress, but that calreticulin is indeed inducible by ER stress [26]. Fig. (1A) shows that calreticulin expression was higher in embryonic heart tissues compared to their adult counterparts. In particular, calreticulin expression diminished dramatically in ventricular tissue postnatally, and remained low into adulthood (Fig. 1, Fig. 4). Earlier studies have demonstrated a role for ER resident chaperones in embryonic development using knockout mice for specific chaperones [10, 27, 28]. Two chaperones, such as calreticulin and Grp94, were found to be critical in embryonic development, as their deficiency induced embryonic death. When calreticulin was ablated, calreticulin-deficient mouse embryos died at gestational day 14.5 as a result of faulty cardiac organogenesis. The cardiac structural defects included very thin ventricular walls with deep intertrabecular recesses [10, 11]. In line with this gene knockout study, our current data showed higher expression of calreticulin in both mouse embryonic atrial and ventricular tissue than in the adult. Calreticulin expression began to subside 17 days postnatally in both atria and ventricles, and in adult ventricles, calreticulin was barely detectable.

Bottom Line: We found stress related chaperones were more abundant in embryonic compared to adult hearts, indicating endoplasmic reticulum stress during normal cardiac development.In adult hearts, chaperones are less abundant but there are increased levels of ATF6alpha and ER stress-activated caspases.Thus, protein synthesis during embryonic development does not seem to be as intense a stress as is required for apoptosis that is found during postnatal remodelling.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.

ABSTRACT
To determine if cardiogenesis causes endoplasmic reticulum stress, we examined chaperone expression. Many cardiac pathologies cause activation of the fetal gene program, and we asked the reverse: could activation of the fetal gene program during development induce endoplasmic reticulum stress/chaperones? We found stress related chaperones were more abundant in embryonic compared to adult hearts, indicating endoplasmic reticulum stress during normal cardiac development. To determine the degree of stress, we investigated endoplasmic reticulum stress pathways during cardiogenesis. We detected higher levels of ATF6alpha, caspase 7 and 12 in adult hearts. Thus, during embryonic development, there is large protein synthetic load but there is no endoplasmic reticulum stress. In adult hearts, chaperones are less abundant but there are increased levels of ATF6alpha and ER stress-activated caspases. Thus, protein synthesis during embryonic development does not seem to be as intense a stress as is required for apoptosis that is found during postnatal remodelling.

No MeSH data available.


Related in: MedlinePlus