2001 Fiscal Year Final Research Report Summary
Abnormality of protein kinase C activity and gap junction activity in diabetic vascular tissues
| Project/Area Number |
11671126
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
INOGUCHI Toyoshi Faculty of medicine, Kyushu University, Associate Prof., 医学部・附属病院, 講師 (00294926)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Keywords | Diabetes / Vascular complication / Gap junction / Connexin / Protein kinase C / Impaired conduction |
|---|
| Research Abstract |
Hyperglycemia appears to be an important etiologic factor in the development of micro- and macrovascular complications in diabetic patients. However, its detailed molecular mechanism remains unclear. Among various possible mechanisms, it is widely accepted that high glucose level and diabetic state induces protein kinase c (PKC) activation in vascular cells in culture and vascular tissues of diabetic animals. Gap junctions are clusters of membrane channels that permit the intercellular exchange of ions and second messengers between adjacent cells. Gap junctional intercellular communication (GJIC) plays an important role in cardiovascular tissue homeostasis. In this study, we report that GJIC in cultured vascular cells such as endothelial cells and smooth muscle cells is inhibited by high glucose level. Furthermore, we show that it is mediated by PKC-dependent excessive phosphorylation of connexin-43 that is the main functional component of gap junction in vascular cells. In addition, it is also shown that, in diabetic rats, PKC-dependent excessive phosphorylation of connexin-43 induces the impairment of ventricular conduction in heart.
In conclusion, these results suggest that PKC -dependent impairment of GJIC may lead to various disorders of cardiovascular homeostasis and contribute to cardiovascular dysfunctions associated with diabetes.
|
