Alda-1 treatment promotes the therapeutic effect of mitochondrial transplantation for myocardial ischemia-reperfusion injury

Sun, Xiaolei; Gao, Rifeng; Li, Wenjia; Zhao, Yongchao; Yang, Heng; Chen, Hang; Jiang, Hao; Dong, Zhen; Hu, Jingjing; Liu, Jin; Zou, Yunzeng; Sun, Aijun; Ge, Junbo

doi:10.1016/j.bioactmat.2020.12.024

Cited by 40 publications

(37 citation statements)

References 52 publications

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“…Using RA-differentiated human SH-SY5Y cells, the present study determined whether transplantation of human plt-mito benefited neuronal survival and mitochondrial function under HR stress, and found that plt-mito transplantation rescued HR-induced mitochondrial malfunction, ROS overproduction and mitochondrial apoptotic pathway. Moreover, plt-mito transplantation increased mitochondrial density of the host cells, which might be associated not only with the supplement of plt-mito, but with enhanced mitochondrial biogenesis following mitochondrial transplantation 28 .…”

Section: Discussionmentioning

confidence: 95%

Platelet Mitochondria Transplantation Rescues Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction and Neuronal Cell Death Involving the FUNDC2/PIP3/Akt/FOXO3a Axis

2021

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Mitochondrial transplantation emerges as a novel therapeutic solution for ischemia/reperfusion injury (IRI) in various tissues. Platelets have recently been used in mitochondrial transplantation as readily-available donors of small-size platelet mitochondria (plt-mito). Interestingly, FUN14 Domain Containing 2 (FUNDC2), a protein highly-expressed in the outer membrane (OMM) of plt-mito, has been identified to maintain platelet survival under hypoxic condition. The current study determined whether and how FUNDC2 contributed to the therapeutic effect of plt-mito transplantation for hypoxia/reoxygenation (HR) injury. The results showed that incorporation of human plt-mito into SH-SY5Y cells rescued HR-induced mitochondrial malfunction and mitochondrial apoptotic pathway. Mechanistically, plt-mito transplantation led to an increased expression of FUNDC2 in the recipient cells. This protein induced mitochondrial translocation of phosphatidylinositol-3,4,5-trisphosphate (PIP3) via its N-term, resulting in the stimulation of the protein kinase B (Akt)/forkhead box O3a (FOXO3a) pathway, which inhibited HR-induced mitochondrial accumulation of a mitochondrial target of FOXO3a, Bim, also known as a pro-apoptotic protein. Therefore, the FUNDC2/PIP3/Akt/FOXO3a axis may facilitate the incorporated plt-mito to restore mitochondrial function and cell viability of the recipient cells, and platelets may serve as readily-available sources of donor mitochondria that afford therapeutic benefits against IRI.

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Section: Discussionmentioning

confidence: 95%

Platelet Mitochondria Transplantation Rescues Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction and Neuronal Cell Death Involving the FUNDC2/PIP3/Akt/FOXO3a Axis

2021

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“…ALDH2 can transform β-aminopropion-aldehyde to β-alanine [ 30 ] and is widely studied as an important cardioprotective factor [ 31 ]. Activate ALDH2 promote mitochondrial homeostasis and suppress mitochondrial ROS (reactive oxygen species) [ 32 , 33 ]. In our results, both MLYCD and ALDH2 was obviously up-regulated that MLYCD may a marker of ROS in central precocious puberty and ALDH2 may play an endogenous protective role.…”

Section: Discussionmentioning

confidence: 99%

The first central precocious puberty proteomic profiles revealed multiple metabolic networks and novel key disease-associated proteins

Wang

Chen

Yuan

et al. 2021

Aging

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“…Mitochondrial dysfunction caused by myocardial ischemia is the main cause of cardiomyocyte death, and reperfusion exacerbates mitochondrial dysfunction. 19 Damaged mitochondria release reactive oxygen species, which lead to mitochondrial protein and DNA damage. This in turn exacerbates mitochondrial dysfunction and forms a vicious cycle.…”

Section: Discussionmentioning

confidence: 99%

JMJD5 attenuates oxygen–glucose deprivation and reperfusion‐induced injury in cardiomyocytes through regulation of HIF‐1α‐BNIP3

Zhang

Pang

Liu

et al. 2021

The Kaohsiung J of Med Scie

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Proteins in Jumonji family function as histone demethylases and participate in cardiac development. Jumonji domain containing 5 (JMJD5) is responsible for the embryonic development through removing methyl moieties from H3K36me2 histone, and has proproliferative effect on heart and eye development. However, the protective role of JMJD5 against oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury in cardiomyocytes has not been fully understood. Firstly, myocardial ischemia/reperfusion (I/R) rat model was established by ligation of left coronary artery. OGD/R was performed in non-transfected H9C2 or H9C2 transfected with pcDNA-JMJD5 plasmid to induce cell cytotoxicity. Data from qRT-PCR and western blot showed that JMJD5 was reduced in the heart tissues of myocardial I/R rat model and OGD/R-induced H9C2. Secondly, JMJD5 over-expression attenuated OGD/R-induced decrease in cell viability and increase in lactate dehydrogenase secretion and cell apoptosis in H9C2. Mitophagy was promoted by pcDNA-mediated over-expression of JMJD5 with enhanced protein expression of LC3-I, LC3-II, Atg5, and Beclin 1. Thirdly, knockdown of JMJD5 aggravated OGD/Rinduced decrease in hypoxia-inducible factor-1α (HIF-1α), whereas JMJD5 overexpression enhanced BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) through upregulation of HIF-1α. Lastly, BNIP3 silencing promoted cell apoptosis, suppressed mitophagy, and attenuated the protective effects of JMJD5 over-expression against OGD/R-induced injury in H9C2. In conclusion, JMJD5 exerted protective effects against OGD/R-induced injury in cardiomyocytes through upregulation of HIF-1α-BNIP3.

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Alda-1 treatment promotes the therapeutic effect of mitochondrial transplantation for myocardial ischemia-reperfusion injury

Cited by 40 publications

References 52 publications

Platelet Mitochondria Transplantation Rescues Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction and Neuronal Cell Death Involving the FUNDC2/PIP3/Akt/FOXO3a Axis

Platelet Mitochondria Transplantation Rescues Hypoxia/Reoxygenation-Induced Mitochondrial Dysfunction and Neuronal Cell Death Involving the FUNDC2/PIP3/Akt/FOXO3a Axis

The first central precocious puberty proteomic profiles revealed multiple metabolic networks and novel key disease-associated proteins

JMJD5 attenuates oxygen–glucose deprivation and reperfusion‐induced injury in cardiomyocytes through regulation of HIF‐1α‐BNIP3

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