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Methylene Blue Alleviates Nuclear and Mitochondrial Abnormalities in Hutchinson‐Gilford Progeria Syndrome
Author(s) -
Xiong Zhengmei,
Choi Ji Young,
Wang Kun,
Zhang Haoyue,
Tariq Zeshan,
Wu Di,
Cao Kan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1100.5
Subject(s) - progeria , lamin , mitochondrion , mitochondrial biogenesis , biology , phenotype , microbiology and biotechnology , premature aging , inner mitochondrial membrane , biogenesis , genetics , gene , nucleus
Hutchinson‐Gilford progeria syndrome (HGPS), a fatal premature aging disease, is caused by a single nucleotide mutation in the lamin A gene. Previous reports have focused on nuclear phenotypes in HGPS cells, and the potential contribution of the mitochondria, a key player in normal aging, remains unclear. Using high‐resolution microscopy analysis, we demonstrated a significantly increased fraction of swollen and fragmented mitochondria and a marked reduction in mitochondrial mobility in HGPS fibroblast cells. Notably, the expression of PGC‐1α, a central regulator of mitochondrial biogenesis, was inhibited by progerin. To rescue mitochondrial defects, we treated HGPS cells with a mitochondrial‐targeting antioxidant methylene blue (MB). Our analysis indicated that MB treatment not only alleviated the mitochondrial defects but also specifically rescued the hallmark nuclear abnormalities in HGPS cells. Additional analysis suggested that MB treatment released progerin from the nuclear membrane, rescued perinuclear heterochromatin loss and corrected misregulated gene expression in HGPS cells. Together, these results demonstrate a role of mitochondrial dysfunction in developing the premature aging phenotypes in HGPS cells and suggest MB as a promising therapeutic for HGPS. Support or Funding Information NIH/NHGRI Grants R01HG007104 (KC) and R21AG043801 (KC)