L-Arginine alleviates heat stress-induced intestinal epithelial barrier damage by promoting expression of tight junction proteins via the AMPK pathway.

Xia Z, Huang L, Yin P, Liu F, Liu Y, Zhang Z, Lin J, Zou W, Li C

Molecular biology reports1 Oct 2019Cited by 51 (Europe PMC)

PMID31576512DOI10.1007/s11033-019-05090-1PepBankPUB-31576512

Summary

Heat stress (HS) and secondary restricted blood flow to the intestines cause dysfunction of the intestinal epithelial barrier. Tight junctions (TJs) are essential to maintain intestinal integrity. L-Arginine has beneficial effects on gut functions. However, the underlying mechanisms remain largely unknown. This study tested the hypothesis that L-arginine regulates the TJ network by activating AMP-activated protein kinase (AMPK) signaling, which in turn improves intestinal barrier functions under HS. IEC-6 cells and rat small intestines were used as experiment models of heat stress. AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively. Cell proliferation, apoptosis, differential gene expression and KEGG pathway analysis, intestinal paracellular permeability, intestinal morphology, and expression of HSP and TJ proteins, and p-AMPK were determined. L-Arginine promoted cell proliferation and reduced apoptosis after heat exposure at an optimal concentration of 5 mmol. Transcriptome sequencing analysis revealed that differentially expressed genes associated with the HSP family and TJs were elevated by L-arginine. According to KEGG pathway analysis, L-arginine activated the AMPK signaling pathway. In vivo, intestinal damage resulted in obvious morphological changes as well as apoptosis with TUNEL and caspase-3 staining under HS and dorsomorphin treatments. Furthermore, HS and dorsomorphin increased the serum D-lactate concentration, diamine oxidase activity, and mRNA expression level of MLCK (P < 0.05). In contrast, L-arginine and AICAR treatments reduced intestinal injury, maintained intestinal permeability, and increased the villus/crypt ratio under hyperthermia. L-Arginine had the same effect as AICAR both in vitro and in vivo, namely increasing p-AMPK protein expression. L-Arginine and AICAR also upregulated the mRNA expression level of HSP70 and HSP90, and downregulated mRNA expression of MLCK (P < 0.05). The protein expression levels of TJ proteins ZO-1 and claudin-1 were suppressed by heat stroke and dorsomorphin, but enhanced by L-arginine and AICAR. Our findings indicate that activation of AMPK signaling by L-arginine is associated with improved intestinal mucosal barrier functions by enhancing the expression of TJs in rat small intestines and IEC-6 cells during HS.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study10

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone10

In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking AICAR (acadesine).

01AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Efficacy outcome
In heat-stressed rat intestines, AICAR reduced intestinal injury.
In plain wordsIn rats under heat stress, AICAR reduced intestinal injury compared with heat stress alone.
Peptide
AICAR (acadesine)
Outcome
DecreaseIntestinal injury
Study
ratn: not reported in source
Heat-stressed rat small intestine
Comparator
Heat stress without AICAR
Outcome group
Gastrointestinal protection · Gastrointestinal
Source sentences
Summary
In contrast, L-arginine and AICAR treatments reduced intestinal injury, maintained intestinal permeability, and increased the villus/crypt ratio under hyperthermia.
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651201
02AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Efficacy outcome
In heat-stressed rat intestines, AICAR maintained intestinal permeability.
In plain wordsIn rats under heat stress, AICAR maintained intestinal permeability compared with heat stress alone.
Peptide
AICAR (acadesine)
Outcome
Direction not reportedIntestinal permeability
Study
ratn: not reported in source
Heat-stressed rat small intestine
Comparator
Heat stress without AICAR
Outcome group
Gastrointestinal protection · Gastrointestinal
Source sentences
Summary
In contrast, L-arginine and AICAR treatments reduced intestinal injury, maintained intestinal permeability, and increased the villus/crypt ratio under hyperthermia.
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651202
03AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Efficacy outcome
In heat-stressed rat intestines, AICAR increased the villus/crypt ratio.
In plain wordsIn rats under heat stress, AICAR increased the villus/crypt ratio compared with heat stress alone.
Peptide
AICAR (acadesine)
Outcome
IncreaseVillus/crypt ratio
Study
ratn: not reported in source
Heat-stressed rat small intestine
Comparator
Heat stress without AICAR
Outcome group
Gastrointestinal protection · Gastrointestinal
Source sentences
Summary
In contrast, L-arginine and AICAR treatments reduced intestinal injury, maintained intestinal permeability, and increased the villus/crypt ratio under hyperthermia.
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651203
04AnimalNot a test of AICAR (acadesine) aloneAnimal study (in vivo)Mechanism
In rat intestines, AICAR increased p-AMPK protein expression.
In plain wordsIn rats, AICAR increased p-AMPK protein expression.
Peptide
AICAR (acadesine)
Outcome
Increasep-AMPK protein expression in vivo
Study
ratn: not reported in source
Heat-stressed rat small intestine
Comparator
Heat stress without AICAR
Outcome group
Receptor activity and mechanism · Gastrointestinal
Source sentences
Summary
L-Arginine had the same effect as AICAR both in vitro and in vivo, namely increasing p-AMPK protein expression.
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651204
05AnimalNot a test of AICAR (acadesine) aloneOther designMechanism
In the rat intestine and IEC-6 study, AICAR increased HSP70 mRNA expression.
In plain wordsIn rat intestines and cells, AICAR increased HSP70 mRNA expression.
Peptide
AICAR (acadesine)
Outcome
IncreaseHSP70 mRNA
Study
ratn: not reported in source
Rat small intestines and IEC-6 cells under heat stress
Comparator
Heat stress without AICAR
Outcome group
Receptor activity and mechanism · Gastrointestinal
Source sentences
Summary
L-Arginine and AICAR also upregulated the mRNA expression level of HSP70 and HSP90, and downregulated mRNA expression of MLCK (P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651206
06AnimalNot a test of AICAR (acadesine) aloneOther designMechanism
In the rat intestine and IEC-6 study, AICAR increased HSP90 mRNA expression.
In plain wordsIn rat intestines and cells, AICAR increased HSP90 mRNA expression.
Peptide
AICAR (acadesine)
Outcome
IncreaseHSP90 mRNA
Study
ratn: not reported in source
Rat small intestines and IEC-6 cells under heat stress
Comparator
Heat stress without AICAR
Outcome group
Receptor activity and mechanism · Gastrointestinal
Source sentences
Summary
L-Arginine and AICAR also upregulated the mRNA expression level of HSP70 and HSP90, and downregulated mRNA expression of MLCK (P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651207
07AnimalNot a test of AICAR (acadesine) aloneOther designMechanism
In the rat intestine and IEC-6 study, AICAR decreased MLCK mRNA expression.
In plain wordsIn rat intestines and cells, AICAR decreased MLCK mRNA expression.
Peptide
AICAR (acadesine)
Outcome
DecreaseMLCK mRNA
Study
ratn: not reported in source
Rat small intestines and IEC-6 cells under heat stress
Comparator
Heat stress without AICAR
Outcome group
Receptor activity and mechanism · Gastrointestinal
Source sentences
Summary
L-Arginine and AICAR also upregulated the mRNA expression level of HSP70 and HSP90, and downregulated mRNA expression of MLCK (P < 0.05).
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651208
08AnimalNot a test of AICAR (acadesine) aloneOther designMechanism
In the rat intestine and IEC-6 study, AICAR enhanced ZO-1 protein expression.
In plain wordsIn rat intestines and cells, AICAR increased ZO-1 protein expression.
Peptide
AICAR (acadesine)
Outcome
IncreaseZO-1 protein expression
Study
ratn: not reported in source
Rat small intestines and IEC-6 cells under heat stress
Comparator
Heat stress without AICAR
Outcome group
Gastrointestinal protection · Gastrointestinal
Source sentences
Summary
The protein expression levels of TJ proteins ZO-1 and claudin-1 were suppressed by heat stroke and dorsomorphin, but enhanced by L-arginine and AICAR.
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651209
09AnimalNot a test of AICAR (acadesine) aloneOther designMechanism
In the rat intestine and IEC-6 study, AICAR enhanced claudin-1 protein expression.
In plain wordsIn rat intestines and cells, AICAR increased claudin-1 protein expression.
Peptide
AICAR (acadesine)
Outcome
IncreaseClaudin-1 protein expression
Study
ratn: not reported in source
Rat small intestines and IEC-6 cells under heat stress
Comparator
Heat stress without AICAR
Outcome group
Gastrointestinal protection · Gastrointestinal
Source sentences
Summary
The protein expression levels of TJ proteins ZO-1 and claudin-1 were suppressed by heat stroke and dorsomorphin, but enhanced by L-arginine and AICAR.
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651210
10LabNot a test of AICAR (acadesine) aloneIn vitro (cells)Mechanism
In IEC-6 cells, AICAR increased p-AMPK protein expression.
In plain wordsIn cells, AICAR increased p-AMPK protein expression.
Peptide
AICAR (acadesine)
Outcome
Increasep-AMPK protein expression in vitro
Study
ratn: not reported in source
Heat-stressed IEC-6 cells
Comparator
Heat stress without AICAR
Outcome group
Receptor activity and mechanism · Gastrointestinal
Source sentences
Summary
L-Arginine had the same effect as AICAR both in vitro and in vivo, namely increasing p-AMPK protein expression.
2 context sentences(design, population, supporting numbers)
Summary · context
IEC-6 cells and rat small intestines were used as experiment models of heat stress.
Summary · context
AICAR and dorsomorphin were used to activate and inhibit the AMPK pathway, respectively.
In this study, AICAR (acadesine) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking AICAR (acadesine).
Show in the study text Report a problemFND-3157651205

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

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