Proteomic and Molecular Assessment of the Common Saudi Variant in ACADVL Gene Through Mesenchymal Stem Cells

被引：9

作者：

Alfares, Ahmad ^{[1
,2
]}

Alfadhel, Majid ^{[3
,4
,5
]}

Mujamammi, Ahmed ^{[6
]}

Alotaibi, Batoul ^{[5
,7
]}

Albahkali, Sarah ^{[5
,7
]}

Al Balwi, Mohammed ^{[2
,4
,5
]}

Benabdelkamel, Hicham ^{[8
]}

Masood, Afshan ^{[8
]}

Ali, Rizwan ^{[5
,9
,10
]}

Almuaysib, Amani ^{[5
,7
]}

Al Mahri, Saeed ^{[5
,11
]}

Mohammad, Sameer ^{[5
,11
]}

Alanazi, Ibrahim O. ^{[12
]}

Alfadda, Assim ^{[8
]}

AlGhamdi, Saleh ^{[4
,13
]}

Alrfaei, Bahauddeen M. ^{[5
,7
]}

机构：

[1] Qassim Univ, Coll Med, Dept Pediat, Al Qassim, Saudi Arabia

[2] King Abdulaziz Med City MNGHA, Dept Pathol & Lab Med, Riyadh, Saudi Arabia

[3] King Abdullah Specialized Children Hosp, Dept Pediat, Div Genet, King Abdulaziz Med City,MNGHA, Riyadh, Saudi Arabia

[4] King Abdullah Int Med Res Ctr, Med Genom Res Dept, MNGHA, Riyadh, Saudi Arabia

[5] King Saud Bin Abduleziz Univ Hlth Sci, Coll Med, MNGHA, Riyadh, Saudi Arabia

[6] King Saud Univ, Coll Med, Dept Pathol, Unit Clin Biochem Med Biochem, Riyadh, Saudi Arabia

[7] King Abdullah Int Med Res Ctr, MNGHA, Dept Cellular Therapy, Stem Cells Unit, Riyadh, Saudi Arabia

[8] King Saud Univ, Coll Med, Obes Res Ctr, Prote Resource Unit, Riyadh, Saudi Arabia

[9] King Abdullah Int Med Res Ctr, Med Core Facil, MNGHA, Riyadh, Saudi Arabia

[10] King Abdullah Int Med Res Ctr, Platforms Dept, MNGHA, Riyadh, Saudi Arabia

[11] King Abdullah Int Med Res Ctr, Dept Expt Med, MNGHA, Riyadh, Saudi Arabia

[12] King Abdulaziz City Sci & Technol, Life Sci & Environm Res Inst, Natl Ctr Biotechnol, Riyadh, Saudi Arabia

[13] King Fahad Med City, Res Ctr, Clin Res Dept, Riyadh, Saudi Arabia

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2020年 / 7卷

关键词：

VLCAD; long-chain fatty acid; mitochondria; mesenchymal stem cells; proteomic; metabolic disorder; COENZYME-A DEHYDROGENASE; COA; DEFICIENCY; MIGRATION;

D O I：

10.3389/fcell.2019.00365

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) is a coenzyme encoded byACADVLthat converts very-long-chain fatty acids into energy. This process is disrupted by c.65C > A; p.Ser22*mutation. To clarify mechanisms by which this mutation leads to VLCAD deficiency, we evaluated differences in molecular and cellular functions between mesenchymal stem cells with normal and mutant VLCAD. Saudi Arabia have a high incidence of this form of mutation. Stem cells with mutant VLCAD were isolated from skin of two patients. Metabolic activity and proliferation were evaluated. The Same evaluation was repeated on normal stem cells introduced with same mutation by CRISPR. Mitochondrial depiction was done by electron microscope and proteomic analysis was done on patients' cells. Metabolic activity and proliferation were significantly lower in patients' cells. Introducing the same mutation into normal stem cells resulted in the same defects. We detected mitochondrial abnormalities by electron microscopy in addition to poor wound healing and migration processes in mutant cells. Furthermore, in a proteomic analysis, we identified several upregulated or downregulated proteins related to hypoglycemia, liver disorder, and cardiac and muscle involvement. We concluded experimental assays of mutantACADVL(c.65C > A; p.Ser22*) contribute to severe neonatal disorders with hypoglycemia, liver disorder, and cardiac and muscle involvement.

引用

页数：12

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