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Perspectives on: SGP symposium on mitochondrial physiology and medicine: mitochondrial proteome design: from molecular identity to pathophysiological regulation.

ABSTRACT:

SUBMITTER: Zhang J

PROVIDER: S-EPMC3362520 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Perspectives on: SGP symposium on mitochondrial physiology and medicine: mitochondrial proteome design: from molecular identity to pathophysiological regulation.

Zhang Jun J Lin Amanda A Powers Jared J Lam Maggie P MP Lotz Christopher C Liem David D Lau Edward E Wang Ding D Deng Ning N Korge Paavo P Zong Nobel C NC Cai Hua H Weiss James J Ping Peipei P

The Journal of general physiology 20120601 6

PMID: 22641634

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Project description:IntroductionEmergency care systems provide timely and relevant care to the acutely ill and injured. Published commentaries have characterised deficiencies in the Nigerian emergency care system and offered potential solutions but have not included the perspectives of the Nigerian public. A more inclusive approach that includes feedback from the public may help improve the Nigerian emergency care system through better understanding of the needs, values and expectations of the community.MethodsParticipants of an emergency medicine symposium participated in focus group discussions that were randomly divided into small groups led by two trained facilitators. These facilitators asked open-ended, semistructured questions to lead discussions in the English language. Participant responses were audio-recorded and transcribed verbatim into transcripts. Two independent investigators employed conventional content analysis to code the transcripts until thematic saturation was achieved.ResultsThree descriptive themes emerged characterising the current state of Nigeria's emergency care system as it relates to prehospital care delivery, hospital care delivery and health system governance: rudimentary, vulnerable and disconnected. At the prehospital level, concepts revolved around emergency recognition and response, ambulance and frontline providers, and cultural norms. At the hospital level, concepts centred around the health workforce, clinical competency, hospital capacity and the burden of financial hardship. At the health system level, concepts concentrated on healthcare access and healthcare financing. Opportunities for emergency care system improvement at each component level were identified and explored.ConclusionsThe participants in this study identified shortcomings and opportunities to improve prehospital care, hospital care and health system governance. The results of this study may help healthcare professionals, policy makers and community leaders identify gaps in the emergency care system and offer solutions in harmony with the needs, values and expectations of the community. If successful, these community-informed interventions may serve as a model to improve emergency care systems throughout Africa.

Project description:BackgroundNeurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is the most widespread NBIA disorder. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) which catalyzes the first reaction of coenzyme A (CoA) biosynthesis. Thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4'-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes.MethodsIn this manuscript, we examined the effect of PANK2 mutations on the expression levels of proteins with phosphopantetheine cofactors in fibroblast derived from PKAN patients. These proteins include cytosolic acyl carrier protein (ACP), which is integrated within the multifunctional polypeptide chain of the fatty acid synthase involved in cytosolic fatty acid biosynthesis type I (FASI); mitochondrial ACP (mtACP) associated with mitocondrial fatty acid biosynthesis type II (FASII); mitochondrial alpha-aminoadipic semialdehyde synthase (AASS); and 10-formyltetrahydrofolate dehydrogenases (cytosolic, ALD1L1, and mitochondrial, ALD1L2).ResultsIn PKAN fibroblasts the expression levels of cytosolic FAS and ALD1L1 were not affected while the expression levels of mtACP, AASS and ALD1L2 were markedly reduced, suggesting that 4'-phosphopantetheinylation of mitochondrial but no cytosolic proteins were markedly affected in PKAN patients. Furthermore, the correction of PANK2 expression levels by treatment with pantothenate in selected mutations with residual enzyme content was able to correct the expression levels of mitochondrial phosphopantetheinyl-proteins and restore the affected pathways. The positive effects of pantothenate in particular mutations were also corroborated in induced neurons obtained by direct reprograming of mutant PANK2 fibroblasts.ConclusionsOur results suggest that the expression levels of mitochondrial phosphopantetheinyl-proteins are severely reduced in PKAN cells and that in selected mutations pantothenate increases the expression levels of both PANK2 and mitochondrial phosphopantetheinyl-proteins associated with remarkable improvement of cell pathophysiology.

Dataset Information

Perspectives on: SGP symposium on mitochondrial physiology and medicine: mitochondrial proteome design: from molecular identity to pathophysiological regulation.

Publications

Perspectives on: SGP symposium on mitochondrial physiology and medicine: mitochondrial proteome design: from molecular identity to pathophysiological regulation.

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