Evidence map›Paper›PMID 25584429›Full record

ArticleToxins2015

Triggering apoptotic death of human epidermal keratinocytes by malic Acid: involvement of endoplasmic reticulum stress- and mitochondria-dependent signaling pathways.

Yu-Ping Hsiao, Wan-Wen Lai, Shi-Bei Wu, Chung-Hung Tsai, Sheau-Chung Tang, Jing-Gung Chung, Jen-Hung Yang

Open access · goldAbstract read
In one paragraph

Article in Toxins, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Organic Acids from Roselle (Biomedicines · 2020
    Review
  6. Review
  7. Dual Effects of Alpha-Hydroxy Acids on the Skin.Molecules (Basel, Switzerland) · 2018
    Review
  8. Article
  9. Nutrient deprivation-related OXPHOS/glycolysis interconversion via HIF-1α/C-MYC pathway in U251 cells.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 5 institutions in 1 country.

Yu-Ping HsiaoInstitute of Medicine, Chung Shan Medical University, 402 Taichung, Taiwan. missyuping@gmail.com.
Wan-Wen LaiInstitute of Medicine, Chung Shan Medical University, 402 Taichung, Taiwan. hauhauma@yahoo.com.tw.
Shi-Bei WuDepartment of Biochemistry and Molecular Biology, National Yang-Ming University, 112 Taipei, Taiwan. labboy700110@gmail.com.
Chung-Hung TsaiInstitute of Medicine, Chung Shan Medical University, 402 Taichung, Taiwan. pathology@csmu.edu.tw.
Sheau-Chung TangDepartment of Dermatology, Buddhist Tzu Chi General Hospital, 907 Hualien, Taiwan. s6160051@yahoo.com.tw.
Jing-Gung ChungSchool of Biological Science and Biotechnology, China Medical University, 404 Taichung, Taiwan. jgchung@mail.cmu.edu.tw.
Jen-Hung YangDepartment of Dermatology, Buddhist Tzu Chi General Hospital, 907 Hualien, Taiwan. jh.med.edu@gmail.com.
Chung Shan Medical University Hospital · TWTzu Chi University · TWChina Medical University · TWChung Shan Medical University · TWNational Yang Ming Chiao Tung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Malic acid (MA) has been commonly used in cosmetic products, but the safety reports in skin are sparse. To investigate the biological effects of MA in human skin keratinocytes, we investigated the potential cytotoxicity and apoptotic effects of MA in human keratinocyte cell lines (HaCaT). The data showed that MA induced apoptosis based on the observations of DAPI staining, DNA fragmentation, and sub-G1 phase in HaCaT cells and normal human epidermal keratinocytes (NHEKs). Flow cytometric assays also showed that MA increased the production of mitochondrial superoxide (mito-SOX) but decreased the mitochondrial membrane potential. Analysis of bioenergetics function with the XF 24 analyzer Seahorse extracellular flux analyzer demonstrated that oxygen consumption rate (OCR) was significantly decreased whereas extracellular acidification rate (ECAR) was increased in MA-treated keratinocytes. The occurrence of apoptosis was proved by the increased expressions of FasL, Fas, Bax, Bid, caspases-3, -8, -9, cytochrome c, and the declined expressions of Bcl-2, PARP. MA also induced endoplasmic reticulum stress associated protein expression such as GRP78, GADD153, and ATF6α. We demonstrated that MA had anti-proliferative effect in HaCaT cell through the inhibition of cell cycle progression at G0/G1, and the induction of programmed cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways.

Indexed as

ApoptosisCaspase 3Cell Cycle CheckpointsCell LineDNA DamageEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressEpidermal CellsHumansKeratinocytesMalatesMitochondriaSignal TransductionCaspase 3Endoplasmic Reticulum Chaperone BiPHSPA5 protein, humanMalatesmalic acid

Identifiers

PMID25584429
PMCPMC4303815
OpenAlexW2042338374

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.