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SHR Neuro Krebs Kardio Lipid

Osibow, K; Frank, S; Malli, R; Zechner, R; Graier, WF.
Mitochondria maintain maturation and secretion of lipoprotein lipase in the endoplasmic reticulum.
Biochem J. 2006; 396(1): 173-182. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Frank Saša
Graier Wolfgang
Malli Roland
Osibow Karin

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Number of Figures: 6
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Considering the physiological Ca2+ dynamics within the ER (endoplasmic reticulum), it remains unclear how efficient protein folding is maintained in living cells. Thus, utilizing the strictly folding-dependent activity and secretion of LPL (lipoprotein lipase), we evaluated the impact of ER Ca2+ content and mitochondrial contribution to Ca2+-dependent protein folding. Exhaustive ER Ca2+ depletion by inhibition of sarcoplasmic/endoplasmic reticulum Ca2+-ATPases caused strong, but reversible, reduction of cell-associated and released activity of constitutive and adenovirus-encoded human LPL in CHO-K1 (Chinese-hamster ovary K1) and endothelial cells respectively, which was not due to decline of mRNA or intracellular protein levels. In contrast, stimulation with the IP3 (inositol 1,4,5-trisphosphate)-generating agonist histamine only moderately and transiently affected LPL maturation in endothelial cells that paralleled a basically preserved ER Ca2+ content. However, in the absence of extracellular Ca2+ or upon prevention of transmitochondrial Ca2+ flux, LPL maturation discontinued upon histamine stimulation. Collectively, these data indicate that Ca2+-dependent protein folding in the ER is predominantly controlled by intraluminal Ca2+ and is largely maintained during physiological cell stimulation owing to efficient ER Ca2+ refilling. Since Ca2+ entry and mitochondrial Ca2+ homoeostasis are crucial for continuous Ca2+-dependent protein maturation in the ER, their pathological alterations may result in dysfunctional protein folding.
Find related publications in this database (using NLM MeSH Indexing)
Adenoviridae - genetics
Animals -
CHO Cells - metabolism
Calcium - physiology
Calcium Signaling -
Calcium-Transporting ATPases - antagonists and inhibitors
Clonazepam - analogs and derivatives Clonazepam - pharmacology
Cricetinae -
Cricetulus -
Endoplasmic Reticulum - metabolism
Endothelial Cells - metabolism
Genetic Vectors -
Histamine - pharmacology
Humans -
Hydroquinones - pharmacology
Inositol 1,4,5-Trisphosphate - agonists
Lipoprotein Lipase - biosynthesis Lipoprotein Lipase - chemistry Lipoprotein Lipase - secretion
Mitochondria - physiology
Protein Folding -
Protein Processing, Post-Translational -
Recombinant Fusion Proteins - metabolism
Thiazepines - pharmacology

Find related publications in this database (Keywords)
Ca2+-dependent protein folding
endoplasmic reticulum
intraluminal Ca2+
lipoprotein lipase
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