Cyclic AMP-dependent protein kinase A plays a role in the directed migration of human keratinocytes in a DC electric field.

Cell motility and the cytoskeleton · 2001 · Unclear · Low evidence

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UnclearLow evidencePaper 3915

Study snapshot

PublicationCell motility and the cytoskeleton · 2001

Study typein_vitro

Reported directionUnclear

Evidence ratingLow

Abstract

Skin wound healing requires epithelial cell migration for re-epithelialization, wound closure, and re-establishment of normal function. We believe that one of the earliest signals to initiate wound healing is the lateral electric field generated by the wound current. Normal human epidermal keratinocytes migrate towards the negative pole, representing the center of the wound, in direct currents of a physiological strength, 100 mV/mm. Virtually nothing is known about the signal transduction mechanisms used by these cells to sense the endogenous electric field. To elucidate possible protein kinase (PK) involvement in the process, PK inhibitors were utilized. Two important findings have been described. Firstly, addition of 50 nM KT5720, an inhibitor of PKA, resulted in a 53% percent reduction in the directional response of keratinocytes in the electric field, while not significantly affecting general cell motility. The reduction was dose-dependent, there was a gradual decrease in the directional response from 5 to 50 nM. Secondly, addition of 1 microM ML-7, a myosin light chain kinase inhibitor, resulted in an approximate 31% decrease in the distance the cells migrated without affecting directional migration. The PKC inhibitors GF109203X at 4 microM and H-7 at 20 microM and W-7, a CaM kinase inhibitor, did not significantly alter either directed migration or cell migration, although they all resulted in a slight reduction in directional migration. D-erythro-sphingosine at 15 microM, a PKC inhibitor, had virtually no effect on either migration distance or directed migration. These findings demonstrate that divergent kinase signaling pathways regulate general cell motility and sustained directional migration and highlight the complexity of the signal transduction mechanisms involved. The inhibitor studies described in this paper implicate a role for PKA in the regulation of the directional migratory response to applied electric fields, galvanotaxis.

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AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro

Effect directionunclear

PopulationNormal human epidermal keratinocytes

Sample sizeNot supplied

ExposureNot supplied

Evidence strengthLowConfidence: 74% · Peer reviewed: yes

Main findings

Normal human epidermal keratinocytes migrated toward the negative pole in a DC electric field of physiological strength (100 mV/mm). The PKA inhibitor KT5720 (50 nM) reduced the directional response by 53% in a dose-dependent manner (5–50 nM) without significantly affecting general motility. The myosin light chain kinase inhibitor ML-7 (1 µM) decreased migration distance by ~31% without affecting directional migration; several PKC and CaM kinase inhibitors showed no significant effects on directed migration or migration distance.

Outcomes measured

Directed migration (directional response) in an applied DC electric field
General cell motility / migration distance

Limitations

Sample size not reported in abstract
In vitro study; relevance to in vivo wound healing not established in abstract
Uses pharmacologic inhibitors; potential off-target effects not addressed in abstract
Exposure duration and other field parameters beyond strength (100 mV/mm) not reported in abstract

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": null,
    "source": "direct current electric field (galvanotaxis assay)",
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": "Normal human epidermal keratinocytes",
  "sample_size": null,
  "outcomes": [
    "Directed migration (directional response) in an applied DC electric field",
    "General cell motility / migration distance"
  ],
  "main_findings": "Normal human epidermal keratinocytes migrated toward the negative pole in a DC electric field of physiological strength (100 mV/mm). The PKA inhibitor KT5720 (50 nM) reduced the directional response by 53% in a dose-dependent manner (5–50 nM) without significantly affecting general motility. The myosin light chain kinase inhibitor ML-7 (1 µM) decreased migration distance by ~31% without affecting directional migration; several PKC and CaM kinase inhibitors showed no significant effects on directed migration or migration distance.",
  "effect_direction": "unclear",
  "limitations": [
    "Sample size not reported in abstract",
    "In vitro study; relevance to in vivo wound healing not established in abstract",
    "Uses pharmacologic inhibitors; potential off-target effects not addressed in abstract",
    "Exposure duration and other field parameters beyond strength (100 mV/mm) not reported in abstract"
  ],
  "evidence_strength": "low",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "keratinocytes",
    "wound healing",
    "galvanotaxis",
    "direct current electric field",
    "PKA",
    "protein kinase inhibitors",
    "directed migration",
    "cell motility"
  ],
  "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1002/cm.10009
PubMed: 11807941

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