Cr supplementation decreases tyrosine phosphorylation of the CreaT in skeletal muscle during sepsis

Weiyang Wang, Michael A. Jobst, Brian Bell, Chun Rui Zhao, Li Hong Shang, Danny O. Jacobs

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Myocellular creatine (Cr) uptake is predominantly governed by a sodium-dependent Cr transporter (CreaT) and plays a pivotal role in skeletal muscle energy metabolism. The CreaT belongs to a neurotransmitter transporter family that can be functionally regulated by protein tyrosine kinase-induced tyrosine phosphorylation. The association between myocellular Cr and c-Src-related tyrosine phosphorylation of the CreaT and the influence of oral Cr supplementation on this association were investigated during sepsis. Animals were randomized to receive standard rat chow or standard rat chow with oral Cr supplementation for 4 days followed by cecal ligation and puncture (CLP) or sham operation. Fast-twitch gastrocnemius muscles were harvested 24 h after operation. Myocellular free Cr levels were 70% higher after CLP. Western blotting of the immunoprecipitated CreaT with an anti-phosphotyrosine or anti-phospho-c-Src (Y-416) antibody revealed that tyrosine phosphorylation of the CreaT and tyrosine-phosphorylated c-Src (Tyr416) expression in the CreaT-c-Src complex were significantly increased after CLP compared with sham operation. These changes were observed in homogenates and plasma membrane fractions of gastrocnemius muscles. Although oral Cr supplementation increased myocellular free Cr levels equivalently in CLP and sham-operated animals, c-Src-related tyrosine phosphorylation of the CreaT in homogenates and plasma membrane fractions of gastrocnemius muscles was, however, downregulated in Cr-supplemented CLP animals compared with Cr-supplemented sham-operated rats. During sepsis, increased myocellular free Cr levels are associated with enhanced tyrosine phosphorylation of the CreaT, which is likely induced by active c-Src. Oral Cr supplementation downregulates c-Src-related tyrosine phosphorylation of the CreaT. The data suggest that myocellular Cr homeostasis and CreaT activity are tightly regulated and closely related during sepsis.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume282
Issue number5 45-5
StatePublished - 2002
Externally publishedYes

Fingerprint

Phosphorylation
Creatine
Tyrosine
Muscle
Sepsis
Skeletal Muscle
Punctures
Ligation
Rats
Animals
Cell membranes
Down-Regulation
Neurotransmitter Transport Proteins
Cell Membrane
Association reactions
Phosphotyrosine
Protein-Tyrosine Kinases
Energy Metabolism
Homeostasis
Western Blotting

Keywords

  • Creatine transporter
  • Phosphorylation
  • Sarcolemma
  • Septic shock
  • Skeletal muscle
  • Src family kinase
  • Tyrosine

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Cr supplementation decreases tyrosine phosphorylation of the CreaT in skeletal muscle during sepsis. / Wang, Weiyang; Jobst, Michael A.; Bell, Brian; Zhao, Chun Rui; Shang, Li Hong; Jacobs, Danny O.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 282, No. 5 45-5, 2002.

Research output: Contribution to journalArticle

Wang, Weiyang ; Jobst, Michael A. ; Bell, Brian ; Zhao, Chun Rui ; Shang, Li Hong ; Jacobs, Danny O. / Cr supplementation decreases tyrosine phosphorylation of the CreaT in skeletal muscle during sepsis. In: American Journal of Physiology - Endocrinology and Metabolism. 2002 ; Vol. 282, No. 5 45-5.
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abstract = "Myocellular creatine (Cr) uptake is predominantly governed by a sodium-dependent Cr transporter (CreaT) and plays a pivotal role in skeletal muscle energy metabolism. The CreaT belongs to a neurotransmitter transporter family that can be functionally regulated by protein tyrosine kinase-induced tyrosine phosphorylation. The association between myocellular Cr and c-Src-related tyrosine phosphorylation of the CreaT and the influence of oral Cr supplementation on this association were investigated during sepsis. Animals were randomized to receive standard rat chow or standard rat chow with oral Cr supplementation for 4 days followed by cecal ligation and puncture (CLP) or sham operation. Fast-twitch gastrocnemius muscles were harvested 24 h after operation. Myocellular free Cr levels were 70{\%} higher after CLP. Western blotting of the immunoprecipitated CreaT with an anti-phosphotyrosine or anti-phospho-c-Src (Y-416) antibody revealed that tyrosine phosphorylation of the CreaT and tyrosine-phosphorylated c-Src (Tyr416) expression in the CreaT-c-Src complex were significantly increased after CLP compared with sham operation. These changes were observed in homogenates and plasma membrane fractions of gastrocnemius muscles. Although oral Cr supplementation increased myocellular free Cr levels equivalently in CLP and sham-operated animals, c-Src-related tyrosine phosphorylation of the CreaT in homogenates and plasma membrane fractions of gastrocnemius muscles was, however, downregulated in Cr-supplemented CLP animals compared with Cr-supplemented sham-operated rats. During sepsis, increased myocellular free Cr levels are associated with enhanced tyrosine phosphorylation of the CreaT, which is likely induced by active c-Src. Oral Cr supplementation downregulates c-Src-related tyrosine phosphorylation of the CreaT. The data suggest that myocellular Cr homeostasis and CreaT activity are tightly regulated and closely related during sepsis.",
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AU - Wang, Weiyang

AU - Jobst, Michael A.

AU - Bell, Brian

AU - Zhao, Chun Rui

AU - Shang, Li Hong

AU - Jacobs, Danny O.

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AB - Myocellular creatine (Cr) uptake is predominantly governed by a sodium-dependent Cr transporter (CreaT) and plays a pivotal role in skeletal muscle energy metabolism. The CreaT belongs to a neurotransmitter transporter family that can be functionally regulated by protein tyrosine kinase-induced tyrosine phosphorylation. The association between myocellular Cr and c-Src-related tyrosine phosphorylation of the CreaT and the influence of oral Cr supplementation on this association were investigated during sepsis. Animals were randomized to receive standard rat chow or standard rat chow with oral Cr supplementation for 4 days followed by cecal ligation and puncture (CLP) or sham operation. Fast-twitch gastrocnemius muscles were harvested 24 h after operation. Myocellular free Cr levels were 70% higher after CLP. Western blotting of the immunoprecipitated CreaT with an anti-phosphotyrosine or anti-phospho-c-Src (Y-416) antibody revealed that tyrosine phosphorylation of the CreaT and tyrosine-phosphorylated c-Src (Tyr416) expression in the CreaT-c-Src complex were significantly increased after CLP compared with sham operation. These changes were observed in homogenates and plasma membrane fractions of gastrocnemius muscles. Although oral Cr supplementation increased myocellular free Cr levels equivalently in CLP and sham-operated animals, c-Src-related tyrosine phosphorylation of the CreaT in homogenates and plasma membrane fractions of gastrocnemius muscles was, however, downregulated in Cr-supplemented CLP animals compared with Cr-supplemented sham-operated rats. During sepsis, increased myocellular free Cr levels are associated with enhanced tyrosine phosphorylation of the CreaT, which is likely induced by active c-Src. Oral Cr supplementation downregulates c-Src-related tyrosine phosphorylation of the CreaT. The data suggest that myocellular Cr homeostasis and CreaT activity are tightly regulated and closely related during sepsis.

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